4,057 results match your criteria Archiv Der Pharmazie[Journal]


Novel benzo[b]xanthene derivatives: Bismuth(III) triflate-catalyzed one-pot synthesis, characterization, and acetylcholinesterase, glutathione S-transferase, and butyrylcholinesterase inhibitory properties.

Arch Pharm (Weinheim) 2020 May 26:e2000030. Epub 2020 May 26.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

In this study, 3,4-dihydro-12-aryl-1H-benzo[b]xanthene-1,6,11-(2H,12H)trione compounds were obtained through one-pot condensation of various substituted aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone, and dimedone in the presence of Bi(OTf) as a green and reusable catalyst. The structural characterization of these novel substituted benzo[b]xanthenes was performed by spectroscopic methods, and their inhibitory actions against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and glutathione S-transferase (GST) were investigated. GST is an enzyme responsible for removing toxic molecules during Phase II reactions in the detoxification mechanism. Read More

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http://dx.doi.org/10.1002/ardp.202000030DOI Listing

Design, synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors.

Arch Pharm (Weinheim) 2020 May 26:e2000060. Epub 2020 May 26.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines. Read More

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http://dx.doi.org/10.1002/ardp.202000060DOI Listing

Aromatase inhibitors: Role in postmenopausal breast cancer.

Arch Pharm (Weinheim) 2020 May 25:e2000081. Epub 2020 May 25.

Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed-to-be-University), New Delhi, India.

Postmenopausal women are at high risk of developing breast cancer due to estrogen production in peripheral tissues of the body other than ovaries. Aromatase is present in breast tissue, leading to local estrogen production which can be inhibited by a variety of steroidal and nonsteroidal aromatase inhibitors. There are many aromatase inhibitors available in clinical practice like exemestane, formestane, anastrozole, letrozole, fadrozole, vorozole, and so forth, but the major challenge in anti-breast cancer therapy is the toxicity associated with aromatase inhibitors, especially the steroidal class of drugs. Read More

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http://dx.doi.org/10.1002/ardp.202000081DOI Listing

Racemic total synthesis and evaluation of the biological activities of the isoquinoline-benzylisoquinoline alkaloid muraricine.

Arch Pharm (Weinheim) 2020 May 25:e2000106. Epub 2020 May 25.

Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University of Munich, Munich, Germany.

The first racemic total synthesis of the isoquinoline-benzylisoquinoline alkaloid muraricine is reported herein. Pharmacological characterization identified muraricine as a moderate inhibitor of P-glycoprotein, a crucial factor of multidrug resistance in cancer. When combined with vincristine, muraricine partly reversed the chemoresistance of vincristine-resistant leukemia cells at a nontoxic concentration. Read More

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http://dx.doi.org/10.1002/ardp.202000106DOI Listing

Novel indole hydrazide derivatives: Synthesis and their antiproliferative activities through inducing apoptosis and DNA damage.

Arch Pharm (Weinheim) 2020 May 17:e2000059. Epub 2020 May 17.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey.

A series of novel indole hydrazide derivatives was synthesized and evaluated for their anticancer activities. Compound 12 exhibited the highest antiproliferative activity against the MCF-7 cell line, with an IC value of 3.01 µM. Read More

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http://dx.doi.org/10.1002/ardp.202000059DOI Listing

2-Aminoaryl-3,5-diaryl pyrazines: Synthesis, biological evaluation against Mycobacterium tuberculosis and docking studies.

Arch Pharm (Weinheim) 2020 May 12:e1900368. Epub 2020 May 12.

Department of Chemistry, Jawaharlal Nehru Technological University, Ananthapuramu, Andhra Pradesh, India.

Rationally designed Mycobacterium tuberculosis (Mtb) inhibitors were synthesized under Buchwald conditions using Pd (dba) /xantphos and the compounds were investigated for their biological activity against the Mtb standard strain H37Rv and two other clinically isolated multidrug-resistant strains with different drug resistance patterns. Compounds 5e, 6e, 7e, and 8e exhibited excellent antituberculosis activity against H37Rv with a minimum inhibitory concentration (MIC) value of 15 μg/ml. Compounds 5a, 6c, 7b, 8a, 8b, and 8d also displayed their potency with a MIC value in the range of 15-25 μg/ml. Read More

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http://dx.doi.org/10.1002/ardp.201900368DOI Listing

Antiproliferative effects of chalcones on T cell acute lymphoblastic leukemia-derived cells: Role of PKCβ.

Arch Pharm (Weinheim) 2020 May 12:e2000062. Epub 2020 May 12.

DISFARM, Sezione di Chimica Generale e Organica "A. Marchesini", Università degli Studi di Milano, Milano, Italy.

In this study, a series of 20 chalcone derivatives was synthesized, and their antiproliferative activity was tested against the human T cell acute lymphoblastic leukemia-derived cell line, CCRF-CEM. On the basis of the structural features of the most active compounds, a new library of chalcone derivatives, according to the structure-activity relationship design, was synthesized, and their antiproliferative activity was tested against the same cancer cell line. Furthermore, four of these derivatives (compounds 3, 4, 8, 28), based on lower IC values (between 6. Read More

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http://dx.doi.org/10.1002/ardp.202000062DOI Listing

Synthesis and biological evaluation of Val-Val dipeptide-sulfonamide conjugates.

Arch Pharm (Weinheim) 2020 May 11:e2000074. Epub 2020 May 11.

Department of Chemical Sciences, Federal University, Wukari, Taraba State, Nigeria.

Novel Val-Val dipeptide-benzenesulfonamide conjugates were reported in this study. These were achieved by a condensation reaction of p-substituted benzenesulfonamoyl alkanamides with 2-amino-4-methyl-N-substituted phenyl butanamide using classical peptide-coupling reagents. The compounds were characterized using Fourier transform infrared, H-nuclear magnetic resonance (NMR), C-NMR, and electrospray ionization-high-resolution mass spectrometry spectroscopic techniques. Read More

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http://dx.doi.org/10.1002/ardp.202000074DOI Listing

Coumarin derivatives with anticancer activities: An update.

Arch Pharm (Weinheim) 2020 May 8:e2000025. Epub 2020 May 8.

State Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China.

Cancer can invade or spread to almost all parts of the body. The increasing morbidity and high mortality of cancer create a great demand for the development of novel anticancer drugs. Coumarin derivatives are ubiquitous in nature and can readily interact with diverse enzymes and receptors in cancer cells via weak bond interactions; hence, coumarin is a highly privileged pharmacophore for the development of novel anticancer agents. Read More

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http://dx.doi.org/10.1002/ardp.202000025DOI Listing
May 2020
1.396 Impact Factor

(E)-2-(2-Allylidenehydrazinyl)thiazole derivatives: Design, green synthesis, in silico and in vitro antimycobacterial and radical scavenging studies.

Arch Pharm (Weinheim) 2020 May 5:e2000003. Epub 2020 May 5.

Organic Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur, Maharashtra, India.

By understanding the rampant infections of Mycobacterium tuberculosis (Mtb) and inflammations caused due to the generation of radical species during the Mtb infection, a series of (E)-2-(2-allylidenehydrazinyl)thiazole derivatives, with dual-action properties, was designed. The molecules were designed with a considerable variation in LogP, one of the critical parameters in physicochemical properties, and analyzed for their drug-likeness. For the synthesis, a simple, green, and multicomponent one-pot synthesis method was developed. Read More

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http://dx.doi.org/10.1002/ardp.202000003DOI Listing

Design and synthesis of new lenalidomide analogs via Suzuki cross-coupling reaction.

Arch Pharm (Weinheim) 2020 Apr 28:e1900376. Epub 2020 Apr 28.

School of Chemistry and Molecular Engineering, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai, China.

Lenalidomide is a cereblon modulator known for its antitumor, anti-inflammatory, and immunomodulatory properties in clinical applications. Recently, some reported lenalidomide analogs could exhibit a significant bioactivity through various modifications in the isoindolinone ring. In this study, we designed and synthesized a series of novel lenalidomide analogs on the basis of the installation of a methylene chain at the C-4 position of isoindolinone via the Suzuki cross-coupling reaction. Read More

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http://dx.doi.org/10.1002/ardp.201900376DOI Listing

Synthesis and biological evaluation of resveratrol derivatives with anti-breast cancer activity.

Arch Pharm (Weinheim) 2020 Apr 28:e2000044. Epub 2020 Apr 28.

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan, China.

Resveratrol is a natural phytoestrogen produced by plants to protect themselves from injury, UV irradiation, and fungal attack. The main active structure is E-resveratrol, which has many pharmacological activities. As the structure of resveratrol is similar to the natural estrogen 17β-estradiol and the synthetic estrogen E-diethylstilbestrol, resveratrol is used in reducing the incidence of breast cancer. Read More

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http://dx.doi.org/10.1002/ardp.202000044DOI Listing

3'-Methyl-4-thio-1H-tetrahydropyranspiro-5'-hydantoin platinum complex as a novel potent anticancer agent and xanthine oxidase inhibitor.

Arch Pharm (Weinheim) 2020 Apr 24:e2000039. Epub 2020 Apr 24.

Department of Chemistry, Faculty of Medicine, University of Nis, Nis, Serbia.

In this study, a Pt(IV) complex with 3'-methyl-4-thio-1H-tetrahydropyranspiro-5'-hydantoin (complex 1) was synthesized. The structure was determined via elemental analyses, infrared, H, and C nuclear magnetic resonance techniques. Density functional theory calculations were applied to optimize the molecular geometry and to calculate structural parameters and vibrational frequencies. Read More

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http://dx.doi.org/10.1002/ardp.202000039DOI Listing

Synthesis, anti-inflammatory activity, and molecular docking studies of some novel Mannich bases of the 1,3,4-oxadiazole-2(3H)-thione scaffold.

Arch Pharm (Weinheim) 2020 Apr 21:e2000061. Epub 2020 Apr 21.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey.

A series of novel ibuprofen and salicylic acid-based 3,5-disubstituted-1,3,4-oxadiazole-2(3H)-thione derivatives was synthesized, and they were evaluated as potential anti-inflammatory agents. Following the structure identification studies employing IR, H nuclear magnetic resonance (NMR), C NMR, and elemental analysis, the title compounds were tested by cyclooxygenase (COX)-1 and COX-2 inhibition assays concomitant to lipopolysaccharide (LPS)-induced nitric oxide and prostaglandin production prevention experiments. The results indicated that the majority of the compounds displayed either a superior or comparable activity in preventing both LPS-induced NO production and COX-1 activity in comparison to the activities of the reference molecules. Read More

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http://dx.doi.org/10.1002/ardp.202000061DOI Listing

Recent progress of 1,3,4-oxadiazoles as anticonvulsants: Future horizons.

Arch Pharm (Weinheim) 2020 Apr 21:e1900342. Epub 2020 Apr 21.

Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research (Formerly Faculty of Pharmacy), Jamia Hamdard, Hamdard Nagar, New Delhi, India.

Epilepsy is the most common neurological disorder, which affects more than 50 million people worldwide. Despite the development and use of several antiepileptic drugs (AEDs), attempted seizure control fails in almost 30% of the individuals treated. Other patients benefit from seizure control by drug therapy at the expense of dose-related toxicity and side effects. Read More

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http://dx.doi.org/10.1002/ardp.201900342DOI Listing

Synthesis, cytotoxicity, and molecular docking of substituted 3-(2-methylbenzofuran-3-yl)-5-(phenoxymethyl)-1,2,4-oxadiazoles.

Arch Pharm (Weinheim) 2020 Apr 20:e2000006. Epub 2020 Apr 20.

Natural Products Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telangana, India.

A series of new benzofuran/oxadiazole hybrids (8a-n) was synthesized from 2H-chromene-3-carbonitriles (3a-c) through the multistep synthetic methodology, and these hybrids are known to exhibit anticancer activities. All the compounds were evaluated for their in vitro cytotoxicity against the HCT116 and MIA PaCa2 cell lines. Compounds 6a (IC : 9. Read More

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http://dx.doi.org/10.1002/ardp.202000006DOI Listing

Catechol-bearing imidazolium and benzimidazolium chlorides as promising antimicrobial agents.

Arch Pharm (Weinheim) 2020 Apr 17:e2000013. Epub 2020 Apr 17.

Department of Chemistry, Faculty of Science, İnönü University, Malatya, Turkey.

Catechol-containing imidazolium (four) and benzimidazolium chlorides (eight) were synthesized to evaluate their antimicrobial properties. All the compounds were fully characterized using H and C nuclear magnetic resonance, liquid chromatography-mass spectrometry, infrared spectroscopic methods, and elemental analyses. Antimicrobial activities of the compounds were tested against the bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. Read More

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http://dx.doi.org/10.1002/ardp.202000013DOI Listing

New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6-(3-Halogenated phenyl-2-propen-1-oyl)-2(3H)-benzoxazolones.

Arch Pharm (Weinheim) 2020 Apr 14:e1900384. Epub 2020 Apr 14.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

In this study, novel halogenated chalcones, 6-(3-halogenated phenyl-2-propen-1-one)-2(3H)-benzoxazolones (2a-n), were synthesized for the first time (except 2a), and their chemical structures were characterized by H nuclear magnetic resonance (NMR), C NMR, and high-resolution mass spectrometry spectra. Cytotoxic activities and carbonic anhydrase (CA) inhibitory effects of the compounds were studied to identify new possible drug candidate molecules. Cytotoxicity results pointed out that compound 2m, 6-[3-(3-bromophenyl)-2-propenoyl]-2(3H)-benzoxazolone, had the highest cytotoxicity (CC ) and potency selectivity expression (PSE) values. Read More

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http://dx.doi.org/10.1002/ardp.201900384DOI Listing

Sulfonamides incorporating ketene N,S-acetal bioisosteres as potent carbonic anhydrase and acetylcholinesterase inhibitors.

Arch Pharm (Weinheim) 2020 Apr 13:e1900383. Epub 2020 Apr 13.

Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, Turkey.

In this study, 15 novel compounds in a series of sulfonamide-based ketenes (7a-o) were synthesized and characterized using Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry. All compounds were tested for their ability to inhibit the human carbonic anhydrase (hCA) isoforms I and II, and acetylcholinesterase (AChE). The halogen-appended compounds, 7g, 7o, and 7i, exhibited the highest hCA I/II and AChE inhibition, with the K values in the low nanomolar range (K  = 9. Read More

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http://dx.doi.org/10.1002/ardp.201900383DOI Listing

Substituted adamantylphthalimides: Synthesis, antiviral and antiproliferative activity.

Arch Pharm (Weinheim) 2020 Apr 14:e2000024. Epub 2020 Apr 14.

Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia.

In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N-(4'-R )phthalimidoadamantanes (1-7), 3-[N-(4'-R )phthalimido]-1-adamantanols (8-10), and 3-[N-(4'-R )phthalimido]adamantane-1-carboxylic acids (11-15), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH substituent at the phthalimide (compounds 3 and 5). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. Read More

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http://dx.doi.org/10.1002/ardp.202000024DOI Listing

Systematic response of staurosporine scaffold-based inhibitors to drug-resistant cancer kinase mutations.

Authors:
Yongkang He

Arch Pharm (Weinheim) 2020 Apr 14:e1900320. Epub 2020 Apr 14.

Department of Infectious Diseases, Taixing People's Hospital, Yangzhou University, Taixing, China.

Human protein kinases have been established as promising druggable targets in cancer therapy. However, a large number of acquired drug-resistant kinase mutations are observed after first- and second-line kinase inhibitor treatments, largely limiting the application of small-molecule inhibitors in the targeted cancer therapy. Previously, the pan-kinase inhibitor staurosporine and its derivatives have been reported to selectively inhibit gatekeeper mutants over wild-type kinases, suggesting that the staurosporine scaffold is potentially helpful in developing wild-type-sparing inhibitors of drug-resistant kinase mutants. Read More

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http://dx.doi.org/10.1002/ardp.201900320DOI Listing

Coumarin-containing hybrids and their antibacterial activities.

Arch Pharm (Weinheim) 2020 Apr 6:e1900380. Epub 2020 Apr 6.

Dong Medicine Key Laboratory of Hunan Province, Department of Laboratory Medicine, Hunan University of Medicine, Huaihua, Hunan, China.

Infections caused by Gram-positive and -negative bacteria are one of the foremost causes of morbidity and mortality globally. Antibiotics are the mainstay of therapy for bacterial infections, but the emergence and wide spread of drug-resistant pathogens have already become a huge issue for public healthcare systems. The coumarin moiety, which is ubiquitous in nature, could bind to the B subunit of DNA gyrase in bacteria and inhibit DNA supercoiling by blocking the ATPase activity; hence, coumarin derivatives possess potential antibacterial activity. Read More

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http://dx.doi.org/10.1002/ardp.201900380DOI Listing
April 2020
1.396 Impact Factor

Substituted 2-thioxothiazolidin-4-one derivatives showed protective effects against diabetic cataract via inhibition of aldose reductase.

Arch Pharm (Weinheim) 2020 Apr 1:e1900371. Epub 2020 Apr 1.

Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinic College of Ophthalmology, Tianjin Eye Hospital, Tianjin Medical University, Tianjin, Heping, China.

In an effort to develop a new class of potent aldose reductase inhibitors against diabetic cataracts, a series of novel 2-thioxothiazolidine-4-one derivatives was synthesized in excellent yields via a facile synthetic route. These compounds were tested against aldehyde (ALR1) and aldose reductase (ALR2) enzymes, where they showed considerable inhibitory activity. Among the tested derivatives, compound 6e showed selective and excellent inhibition of ALR2 over ALR1. Read More

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http://dx.doi.org/10.1002/ardp.201900371DOI Listing

New thiazolyl-pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents.

Arch Pharm (Weinheim) 2020 May 18;353(5):e1900351. Epub 2020 Mar 18.

Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, Cali, Colombia.

A new series of N-substituted pyrazoline derivatives 6a-g, 7a-g, 8a-g, and 9a-g was synthetized by reaction of hydrazine derivatives and chalcone-thiazole hybrids bearing nitrogen mustard 5a-g. The chalcones 5a-g were obtained by Claisen-Schmidt condensation of thiazole-2-nitrogen mustard 3 and selected acetophenones 4a-g. These new compounds 6/7/8/9a-g were screened for their antifungal activity against Cryptococcus neoformans, with IC values of 3. Read More

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http://dx.doi.org/10.1002/ardp.201900351DOI Listing

Synthesis and leishmanicidal evaluation of sulfanyl- and sulfonyl-tethered functionalized benzoate derivatives featuring a nitroimidazole moiety.

Arch Pharm (Weinheim) 2020 May 16;353(5):e2000002. Epub 2020 Mar 16.

Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Univ. Central de Venezuela, Caracas, Venezuela.

A series of new nitroimidazole-containing derivatives was synthesized by coupling of 2-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio]ethanol with diversely substituted benzoic acids. Upon treatment with m-CPBA, 12 of these sulfanyl compounds were further oxidized to their sulfonyl analogs. All the 26 synthetic compounds were examined for in vitro activity against Leishmania (V. Read More

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http://dx.doi.org/10.1002/ardp.202000002DOI Listing

Structure-based design, synthesis, and evaluation of Bcl-2/Mcl-1 dual inhibitors.

Arch Pharm (Weinheim) 2020 May 16;353(5):e2000005. Epub 2020 Mar 16.

State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian, China.

Based on our previously reported Bcl-2/Mcl-1 dual inhibitor 4-thiomorpholinyl-2-cyano-3-amidinophenalenone (A1) that simultaneously occupies the p2 and p4 hydrophobic pockets of Bcl-2 and Mcl-1, we optimized molecules with different bond angles of the groups extending to the p4 pocket and bulky hydrophobic groups to explore p2. Research on structure-activity relationship resulted in a new derivative B4 that is capable of occupying both the p2 and p4 more deeply and completely than A1, with K values determined by fluorescence polarization assay (FPAs) improving to 0.31 μM for Bcl-2 and 0. Read More

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http://dx.doi.org/10.1002/ardp.202000005DOI Listing

Synthesis and docking study of benzimidazole-triazolothiadiazine hybrids as aromatase inhibitors.

Arch Pharm (Weinheim) 2020 May 11;353(5):e2000008. Epub 2020 Mar 11.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

Aromatase is involved in the biosynthesis of estrogen and thus is a critical target for breast cancer. In this study, to identify new aromatase enzyme inhibitors, seven 3-[4-(5-methyl-1H-benzo[d]imidazol-2-yl)phenyl]-6-(substituted phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives were synthesized. First, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the inhibitory activity of the synthesized compounds on the MCF-7 cell line. Read More

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http://dx.doi.org/10.1002/ardp.202000008DOI Listing

Evaluation of the antiparasitic activities of imidazol-2-ylidene-gold(I) complexes.

Arch Pharm (Weinheim) 2020 May 9;353(5):e1900363. Epub 2020 Mar 9.

Organic Chemistry Laboratory, University of Bayreuth, Bayreuth, Germany.

A series of cationic gold(I)-carbene complexes with various 4,5-diarylimidazolylidene ligands were either newly prepared or repurposed for testing against protozoal Leishmania major, Toxoplasma gondii, and Trypanosoma brucei parasites. The syntheses of the new complexes 1b and 1c were described. Ferrocene compound 1a showed the highest activities against L. Read More

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http://dx.doi.org/10.1002/ardp.201900363DOI Listing

Synthesis of imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives as inhibitors of virulence factors production in Pseudomonas aeruginosa.

Arch Pharm (Weinheim) 2020 May 5;353(5):e1900352. Epub 2020 Mar 5.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudomonas aeruginosa, including protease, hemolysin, and pyocyanin. Imidazolidine-2,4-diones 4c, 4j, and 12a showed complete inhibition of the protease enzyme, and they almost completely inhibited the production of hemolysin at 1/4 MIC (1/4 minimum inhibitory concentration; 1, 0. Read More

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http://dx.doi.org/10.1002/ardp.201900352DOI Listing

Recent advances with alkaline phosphatase isoenzymes and their inhibitors.

Arch Pharm (Weinheim) 2020 May 4;353(5):e2000011. Epub 2020 Mar 4.

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan.

Alkaline phosphatases are found in different living species and play crucial roles in various significant functions, such as hydrolyzing a variable spectrum of phosphate-containing physiological compounds, contributing to DNA synthesis, bone calcification, and attenuation of inflammation. They are homodimeric enzymes; each subunit contains one magnesium ion and two zinc ions crucial for the catalytic activity of the enzyme. Alkaline phosphatases exist in four distinct isoenzymes (placental, intestinal, germ cell, and tissue nonspecific alkaline phosphatases), which are expressed by four different genes; each one of them has distinguished functions. Read More

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http://dx.doi.org/10.1002/ardp.202000011DOI Listing
May 2020
1.396 Impact Factor

Methylene-bearing sulfur-containing cyanopyrimidine derivatives for treatment of cancer: Part-II.

Arch Pharm (Weinheim) 2020 May 2;353(5):e1900333. Epub 2020 Mar 2.

Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research (Formerly Faculty of Pharmacy), Jamia Hamdard, New Delhi, India.

In continuation of our previous work on anticancer and anti-inflammatory agents, a series of 22 novel methylene-bearing sulfur-containing cyanopyrimidine derivatives was synthesized by Biginelli condensation reaction, which was followed by nucleophilic substitution of the chloro group with secondary or tertiary amines. Structural confirmation of these derivatives was attained through different spectral techniques. Then, anticancer evaluation of these compounds was done at the National Cancer Institute. Read More

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http://dx.doi.org/10.1002/ardp.201900333DOI Listing

Novel pyrazolopyrimidine urea derivatives: Synthesis, antiproliferative activity, VEGFR-2 inhibition, and effects on the cell cycle profile.

Arch Pharm (Weinheim) 2020 Apr 24;353(4):e1900319. Epub 2020 Feb 24.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

A series of novel diaryl urea pyrazolopyrimidine derivatives was designed and synthesized. All the synthesized compounds were evaluated for cytotoxic activity by the National Cancer Institute. A significant antiproliferative activity at a 10-µM dose was shown by four compounds (5c, 5e, 5g, and 5h), and they were accordingly evaluated at five concentrations. Read More

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http://dx.doi.org/10.1002/ardp.201900319DOI Listing

Novel pyrazolo[3,4-d]pyrimidine derivatives inhibit human cancer cell proliferation and induce apoptosis by ROS generation.

Arch Pharm (Weinheim) 2020 Apr 19;353(4):e1900296. Epub 2020 Feb 19.

Department of Studies in Chemistry, Karnatak University, Dharwad, Karnataka, India.

The paucity of effective anticancer drugs for successful treatment is a major concern, indicating the strong need for novel therapeutic compounds. In the quest of new molecules, the present study aimed to explore the potential of pyrazolo[3,4-d]pyrimidine derivatives as antiproliferative agents. In vitro anticancer screening of selected compounds was done by the National Cancer Institute's Developmental Therapeutics Programme against a panel of 60 cancer cell lines. Read More

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http://dx.doi.org/10.1002/ardp.201900296DOI Listing

Design, synthesis, and molecular docking of novel 2-arylbenzothiazole multiangiokinase inhibitors targeting breast cancer.

Arch Pharm (Weinheim) 2020 Apr 11;353(4):e1900340. Epub 2020 Feb 11.

Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, Cairo, Egypt.

A novel series of 2-arylbenzothiazoles 9, 10, and 12 were designed and synthesized as VEGFR-2/FGFR-1/PDGFR-β multiangiokinase inhibitors targeting breast cancer. Structural elongation of the known 2-phenylbenzothiazole scaffold (type I protein kinase inhibitor [PKI]), was carried out to afford series of type II PKIs 9, 10, and 12. Compounds 9d, 9f, 9i, and 9k exhibited potent multikinase inhibitory activity with IC values of 0. Read More

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http://dx.doi.org/10.1002/ardp.201900340DOI Listing
April 2020
1.396 Impact Factor

Synthesis and biological evaluation of pyrazolone analogues as potential anti-inflammatory agents targeting cyclooxygenases and 5-lipoxygenase.

Arch Pharm (Weinheim) 2020 Apr 7;353(4):e1900308. Epub 2020 Feb 7.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

New pyrazolone derivatives structurally related to celecoxib and FPL 62064 were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases (COXs) and 5-lipoxygenase (5-LOX) and their selectivity indices were calculated. The results showed that compounds 3f, 3h, 3l, and 3p have an excellent COX-2 selectivity index. Moreover, they showed potent 5-LOX inhibitory activity relative to celecoxib and zileuton, as positive controls. Read More

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http://dx.doi.org/10.1002/ardp.201900308DOI Listing

Chalcone hybrids and their antimalarial activity.

Arch Pharm (Weinheim) 2020 Apr 31;353(4):e1900350. Epub 2020 Jan 31.

Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, Shandong, China.

Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Read More

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http://dx.doi.org/10.1002/ardp.201900350DOI Listing

3'-(4-(Benzyloxy)phenyl)-1'-phenyl-5-(heteroaryl/aryl)-3,4-dihydro-1'H,2H-[3,4'-bipyrazole]-2-carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies.

Arch Pharm (Weinheim) 2020 Apr 31;353(4):e1900262. Epub 2020 Jan 31.

Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.

Pyrazoline-linked carboxamide derivatives were designed, synthesized, and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer activity, and apoptotic and cardiomyopathy toxicity. Compounds 6m and 6n inhibit EGFR kinase at a concentration of 6.5 ± 2. Read More

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http://dx.doi.org/10.1002/ardp.201900262DOI Listing

A new sensitive and subunit-selective molecular tool for investigating protein kinase A in the brain.

Arch Pharm (Weinheim) 2020 Apr 29;353(4):e1900326. Epub 2020 Jan 29.

Biostructures and Biosystems National Institute, Rome, Italy.

Despite cellular complexity, a limited number of small molecules act as intracellular second messengers. Protein kinase A (PKA) is the main transducer of the information carried by cyclic adenosine monophosphate (cAMP). Recently, cellular imaging has achieved major technical advancements, although the search for more specific and sensitive low-molecular-weight probes to explore subcellular events involving second messengers is still in progress. Read More

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http://dx.doi.org/10.1002/ardp.201900326DOI Listing

Synthesis, crystal structure, and ADME prediction studies of novel imidazopyrimidines as antibacterial and cytotoxic agents.

Arch Pharm (Weinheim) 2020 Mar 27;353(3):e1900271. Epub 2020 Jan 27.

Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries Research, National Research Centre, Cairo, Egypt.

In the present study, a novel series of polyfunctionalized imidazopyrimidines 6a-u and 9a-d were efficiently constructed by a domino reaction between 2-imino-6-substituted-2,3-dihydropyrimidin-4(1H)-ones 4a-d or 8a-c and 2-bromoacetophenones 5a-i under mild basic conditions. The synthesized series were screened for their antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive (+) bacteria, as well as against Gram-negative (-) bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhi. Most of the synthesized derivatives of imidazopyrimidines 6 and 9 showed remarkable selectivity against Gram(-) bacteria over the Gram(+) ones. Read More

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http://dx.doi.org/10.1002/ardp.201900271DOI Listing
March 2020
1.396 Impact Factor

Isatin dimers and their biological activities.

Arch Pharm (Weinheim) 2020 Mar 27;353(3):e1900299. Epub 2020 Jan 27.

Teaching and Research Office of Analytical Chemistry, School of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guizhou, China.

Dimerization is a promising strategy to develop novel drug candidates that could extend the biological spectrum, enhance the activity, overcome drug resistance, as well as improve pharmacological, pharmacokinetic, and physicochemical profiles. Isatin dimers possess a broad spectrum of biological properties and the isatin dimer indirubin has already been used in the clinic, revealing the potential of isatin dimers as putative drugs. This review covers the recent advances of isatin dimers as pharmacologically significant scaffolds and the structure-activity relationship to set up the direction for the design and development of isatin dimers with higher efficiency and lower toxicity. Read More

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http://dx.doi.org/10.1002/ardp.201900299DOI Listing

Synthesis, in-vitro and in-silico study of novel thiazoles as potent antibacterial agents and MurB inhibitors.

Arch Pharm (Weinheim) 2020 Apr 22;353(4):e1900309. Epub 2020 Jan 22.

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

Efficient procedures are herein reported for the synthesis of novel hybrid thiazoles via a one-pot three-component protocol. The protocol involves the reaction of novel aldehyde, thiosemicarbazide and halogen-containing reagents in solvent- and catalyst-free conditions. The structures of the new thiazoles were elucidated by elemental analyses and spectroscopic data. Read More

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http://dx.doi.org/10.1002/ardp.201900309DOI Listing

Recent advances in isatin hybrids as potential anticancer agents.

Arch Pharm (Weinheim) 2020 Mar 21;353(3):e1900367. Epub 2020 Jan 21.

Department of Pharmacy, Bozhou People's Hospital, Bozhou, China.

The isatin framework is a useful template for the development of novel anticancer agents. This is exemplified by the fact that several isatin-based anticancer agents, such as semaxanib, sunitinib, nintedanib, and hesperadin, are already in use or under clinical trials for the treatment of diverse kinds of cancers. Isatin-based hybrids could be obtained by incorporating other anticancer pharmacophores into the isatin skeleton and they have the potential to overcome drug resistance with reduced side effects. Read More

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http://dx.doi.org/10.1002/ardp.201900367DOI Listing

Synthesis and biological screening of some novel 6-substituted 2-alkylpyridazin-3(2H)-ones as anti-inflammatory and analgesic agents.

Arch Pharm (Weinheim) 2020 Mar 15;353(3):e1900295. Epub 2020 Jan 15.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.

Some novel derivatives of 2-alkyl 6-substituted pyridazin-3(2H)-ones were synthesized by condensation of 3,6-dichloropyridazine with the sodium salt of benzyl cyanide, followed by hydrolysis and coupling with alkyl halides. The synthesized compounds were screened as cyclooxygenase (COX)-1/COX-2 inhibitors and as analgesic and anti-inflammatory agents. Among the synthesized compounds, 6-benzyl-2-methylpyridazin-3(2H)-one (4a), 6-benzoyl-2-propylpyridazin-3(2H)-one (8b), and 6-(hydroxy(phenyl)methyl)-2-methylpyridazin-3(2H)-one (9a) displayed the highest COX-2 selectivity indices of 96, 99, and 98, respectively, and analgesic efficacies of 47%, 46%, and 45% protection, respectively. Read More

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http://dx.doi.org/10.1002/ardp.201900295DOI Listing

Synthesis and characterization of some new pyrazolines and their inhibitory potencies against carbonic anhydrases.

Arch Pharm (Weinheim) 2020 Mar 10;353(3):e1900292. Epub 2020 Jan 10.

Department of Agricultural Biotechnology, Faculty of Agriculture, Ondokuz Mayıs University, Samsun, Turkey.

The inhibition of the two human cytosolic carbonic anhydrase (hCA; EC 4.2.1. Read More

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http://dx.doi.org/10.1002/ardp.201900292DOI Listing

rac- and meso-Cyclohexanoids: Their α-, β-glycosidases, antibacterial, antifungal activities, and molecular docking studies.

Arch Pharm (Weinheim) 2020 Mar 10;353(3):e1900267. Epub 2020 Jan 10.

Department of Chemistry, Sakarya University, Sakarya, Turkey.

An efficient and versatile synthesis method has been postulated for hydroxymethylated rac- and meso-cyclohexanoid derivatives. The synthesis of these stereoisomers was achieved easily with traditional methods using hexahydroisobenzofuran 6, prepared from commercially available cis-hydrophthalic anhydride. The study, involving diastereoselective epoxidation and cis-hydroxylation, was conducted to obtain epoxy-, cis-, and trans-diol-furans 7, 8, and 9. Read More

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http://dx.doi.org/10.1002/ardp.201900267DOI Listing

Design, synthesis, and biological evaluation of new 1,4-diarylazetidin-2-one derivatives (β-lactams) as selective cyclooxygenase-2 inhibitors.

Arch Pharm (Weinheim) 2020 Mar 9;353(3):e1900293. Epub 2020 Jan 9.

Department of Pharmaceutical Chemistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

A new series of 1,4-diarylazetidin-2-one derivatives (β-lactams) were designed and synthesized to evaluate their biological activities as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that all compounds were selective inhibitors of the COX-2 isozyme with IC values in the 0.05-0. Read More

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http://dx.doi.org/10.1002/ardp.201900293DOI Listing

Propafenone analogue with additional H-bond acceptor group shows increased inhibitory activity on P-glycoprotein.

Arch Pharm (Weinheim) 2020 Mar 9;353(3):e1900269. Epub 2020 Jan 9.

Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.

P-glycoprotein (P-gp) is an ATP-dependent efflux pump that has a marked impact on the absorption, distribution, and excretion of therapeutic drugs. As P-gp inhibition can result in drug-drug interactions and altered drug bioavailability, identifying molecular properties that are linked to inhibition is of great interest in drug development. In this study, we combined chemical synthesis, in vitro testing, quantitative structure-activity relationship analysis, and docking studies to investigate the role of hydrogen bond (H-bond) donor/acceptor properties in transporter-ligand interaction. Read More

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http://dx.doi.org/10.1002/ardp.201900269DOI Listing

Pharmacophore modeling, 3D-QSAR, synthesis, and anti-lung cancer evaluation of novel thieno[2,3-d][1,2,3]triazines targeting EGFR.

Arch Pharm (Weinheim) 2020 Feb 2;353(2):e1900108. Epub 2020 Jan 2.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.

Two series of thieno[2,3-d][1,2,3]triazine derivatives were designed, synthesized, and biologically evaluated as potential epidermal growth factor receptor (EGFR) inhibitors targeting the non-small-cell lung cancer cell line H1299. Most of the synthesized compounds displayed IC values ranging from 25 to 58 nM against H1299, which are superior to that of gefitinib (40 µM). 3-(5,6,7,8-Tetrahydro-7H-cyclohexa[4:5]thieno[2,3-d]-1,2,3-triazin-4-ylamino)benzene-1,3-diamine (6b) achieved the highest cytotoxic activity against H1299 with an IC value of 25 nM; it had the ability to decrease the EGFR concentration in H1299 cells from 7. Read More

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http://dx.doi.org/10.1002/ardp.201900108DOI Listing
February 2020

Exploration of (3-benzyl-5-hydroxyphenyl)carbamates as new antibacterial agents against Gram-positive bacteria.

Arch Pharm (Weinheim) 2020 Mar 2;353(3):e1900294. Epub 2020 Jan 2.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

A series of (3-benzyl-5-hydroxyphenyl)carbamates were evaluated as new antibacterial agents. Several compounds showed potent inhibitory activity against sensitive and drug-resistant Gram-positive bacteria. The compounds are ineffective against all tested Gram-negative bacteria. Read More

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http://dx.doi.org/10.1002/ardp.201900294DOI Listing

Synthesis and anti-inflammatory effects of novel emodin derivatives bearing azole moieties.

Arch Pharm (Weinheim) 2020 Feb 30;353(2):e1900264. Epub 2019 Dec 30.

Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, China.

Twelve azole derivatives of emodin were designed to possess anti-inflammatory activity and synthesized via a two-step sequence composed of the Williamson ether reaction and N-alkylation. The anti-inflammatory properties of these compounds were evaluated in RAW264.7 cells by measuring lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Read More

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http://dx.doi.org/10.1002/ardp.201900264DOI Listing
February 2020