4,356 results match your criteria Archiv Der Pharmazie[Journal]


Novel isoxazoline-linked 1,3,4-thiadiazole hybrids as anticancer agents: Design, synthesis, biological evaluation, molecular docking, and molecular dynamics simulation.

Arch Pharm (Weinheim) 2022 May 20:e2200066. Epub 2022 May 20.

Laboratory of Organic Synthesis and Physico-Molecular Chemistry, Department of Chemistry, Faculty of Sciences Semlalia, Marrakesh, Morocco.

In the current study, natural (R)-carvone was utilized as a starting material for the efficient synthesis of two series of isoxazoline derivatives bearing the 1,3,4-thiadiazole moiety. The new compounds were obtained in good yields and were characterized by H and C NMR and HRMS analysis. The newly synthesized monoterpenic isoxazoline 1,3,4-thiadiazole and their thiosemicarbazone intermediate derivatives were evaluated for their anticancer activity in four cancer cell lines (HT-1080, A-549, MCF-7, and MDA-MB-231). Read More

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Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5-nitrothiophene derivatives for anticancer activity.

Arch Pharm (Weinheim) 2022 May 18:e2200105. Epub 2022 May 18.

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

Within the scope of this study, new 2-{2-[(5-nitrothiophen-2-yl)methylene]hydrazinyl}thiazole derivatives (2a-j) were synthesized and investigated for their potential anticancer and enzyme inhibition activities. Spectroscopic techniques were used to determine the structures of substances. The anticancer activities of compounds were detected in A549 human lung carcinoma and L929 murine fibroblast cell lines, determining cytotoxicity, apoptosis, mitochondrial membrane integrity, and caspase-3 activation. Read More

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Oxadiazole: A highly versatile scaffold in drug discovery.

Arch Pharm (Weinheim) 2022 May 16:e2200123. Epub 2022 May 16.

Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India.

As a pharmacologically important heterocycle, oxadiazole paved the way to combat the problem associated with the confluence of many commercially available drugs with different pharmacological profiles. The present review focuses on the potential applications of five-membered heterocyclic oxadiazole derivatives, especially 1,2,4-oxadiazole, 1,2,5-oxadiazole, and 1,3,4-oxadiazole, as therapeutic agents. Designing new hybrid molecules containing the oxadiazole moiety is a better solution for the development of new drug molecules. Read More

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Revealing the role of the benzyloxy pharmacophore in the design of a new class of monoamine oxidase-B inhibitors.

Arch Pharm (Weinheim) 2022 May 13:e2200084. Epub 2022 May 13.

Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, India.

The conceptual layout of monoamine oxidase (MAO) inhibitors has been modified to explore their potential biological application in the case of neurological disorders for the time being. The current review article is an effort to display the summation of innovative conceptual prospects of MAO inhibitors and their intriguing chemistry and bioactivity. Based on this scenario, we emphasize the pivotal role of the benzyloxy moiety attached to scaffolds like oxadiazolones, indolalkylamines, safinamide, caffeine, benzofurans, α-tetralones, β-nitrostyrene, benzoquinones, coumarins, indoles, chromones, and chromanone analogs, while acting as an MAO inhibitor. Read More

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Selective cytotoxicity of ent-kaurene diterpenoids isolated from Baccharis lateralis and Baccharis retusa (Asteraceae).

Arch Pharm (Weinheim) 2022 May 12:e2200083. Epub 2022 May 12.

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, São Paulo, Brazil.

This study presents the cytotoxic activity evaluation of the natural diterpenes ent-kaurenoic acid (1) and its 15β-hydroxy (2), 15β-senecioyloxy (3), and 15β-tiglinoyloxy (4) derivatives, isolated from Brazilian native plants, Baccharis retusa and B. lateralis (Asteraceae). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay, it was observed that compound 1 displayed in vitro activity towards the aggressive MDA-MB-231 adenocarcinoma cell line and reduced toxicity against MCF-10A nontumorigenic epithelial cells, indicating expressive selectivity. Read More

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Exploring ibuprofen derivatives as α-glucosidase and lipoxygenase inhibitors: Cytotoxicity and in silico studies.

Arch Pharm (Weinheim) 2022 May 9:e2200013. Epub 2022 May 9.

Department of Chemistry, Hazara University, Mansehra, Pakistan.

This study reports the synthesis of a series of ibuprofen derivatives, including thiosemicarbazides 4a-f, 1,3,4-oxadiazoles 5a-f, 1,3,4-thiadiazoles 6a-f, 1,2,4-triazoles 7a-f, and their S-alkylated derivatives 8a-d. All of the newly synthesized derivatives were analyzed using H NMR, C NMR spectroscopy, and high-resolution mass spectra (electron ionization) spectrometry. These synthetic molecules were examined for their in vitro baking yeast α-glucosidase and soybean 15-lipoxygenase (15-LOX) inhibition and cell viability studies. Read More

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Therapeutic potential of 1,2,3-triazole hybrids for leukemia treatment.

Arch Pharm (Weinheim) 2022 May 9:e2200106. Epub 2022 May 9.

Emergency Department, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang, China.

Leukemia, a hematological malignancy originating from the bone marrow, is the principal cancer of childhood. In recent decades, improved remission rates and survival of patients with leukemia have been achieved due to significant breakthroughs in the treatment. However, chemoresistance and relapse are common, creating an urgent need for the search for novel pharmaceutical interventions. Read More

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Quinoxaline-based efflux pump inhibitors restore drug susceptibility in drug-resistant nontuberculous mycobacteria.

Arch Pharm (Weinheim) 2022 May 9:e2100492. Epub 2022 May 9.

Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.

Nontuberculous mycobacteria (NTM) comprise several ubiquitous, environmentally localized bacteria that may be responsible for serious human diseases. NTM-associated pulmonary infections largely affect individuals with underlying respiratory disease or chronic disease and immunosuppressed patients. Mycobacterium simiae and M. Read More

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Anti-inflammatory activity of pyridazinones: A review.

Arch Pharm (Weinheim) 2022 May 9:e2200067. Epub 2022 May 9.

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

The pyridazinone core has emerged as a leading structure for fighting inflammation, with low ulcerogenic effects. Moreover, easy functionalization of various ring positions of the pyridazinone core structure makes it an attractive synthetic and therapeutic target for the design and synthesis of anti-inflammatory agents. The present review surveys the recent advances of pyridazinone derivatives as potential anti-inflammatory agents to provide insights into the rational design of more effective anti-inflammatory pyridazinones. Read More

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ω-(5-Phenyl-2H-tetrazol-2-yl)alkyl-substituted hydrazides and related compounds as inhibitors of amine oxidase copper containing 3 (AOC3).

Arch Pharm (Weinheim) 2022 May 4:e2200111. Epub 2022 May 4.

Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, Germany.

Amine oxidase copper containing 3 (AOC3), also known as plasma amine oxidase, semicarbazide-sensitive amine oxidase, or vascular adhesion protein-1, catalyzes the oxidative deamination of primary amines to aldehydes using copper and a quinone as cofactors. Because it is involved in the transmigration of inflammatory cells through blood vessels into tissues, AOC3 is thought to play an important role in inflammatory diseases. Therefore, inhibitors of this enzyme could lead to new therapeutics for the treatment of inflammation-related diseases. Read More

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Design, synthesis, and biological activity of novel dithiocarbamate-methylsulfonyl hybrids as carbonic anhydrase inhibitors.

Arch Pharm (Weinheim) 2022 May 3:e2200132. Epub 2022 May 3.

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

Carbonic anhydrase (CA) enzymes are involved in many physiological events. These enzymes, which contain Zn in their structure, can be easily inhibited by dithiocarbamate compounds. In addition, CA enzyme inhibitory activities are known in groups such as sulfonamide and methylsulfonyl. Read More

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New 1H-indole-2,3-dione 3-thiosemicarbazones with 3-sulfamoylphenyl moiety as selective carbonic anhydrase inhibitors.

Arch Pharm (Weinheim) 2022 May 2:e2200023. Epub 2022 May 2.

Health Sciences Institute, Istanbul University, Istanbul, Turkey.

1-Methyl/ethyl/benzyl-5-(un)substituted 1H-indole-2,3-diones (2, 3, and 4) were synthesized by reaction of 5-(un)substituted 1H-indole-2,3-diones (1) with methyl iodide, ethyl chloride, and benzyl bromide. (3-Sulfamoylphenyl)isothiocyanate (6) was obtained by the treatment of 3-aminobenzenesulfonamide (5) with thiophosgene. Compound 6 was reacted with hydrazine to yield 4-(3-sulfamoylphenyl)thiosemicarbazide (7). Read More

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Development and molecular modeling studies of new thiadiazole piperazine urea derivatives as potential fatty acid amide hydrolase inhibitors.

Arch Pharm (Weinheim) 2022 May 2:e2200082. Epub 2022 May 2.

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

A series of novel piperazine urea derivatives with thiadiazole moieties were designed, synthesized, and investigated for their inhibition potential against human fatty acid amide hydrolase (hFAAH). The urea derivatives possessing p-chlorophenylthiadiazole and benzylpiperazine fragments (19-22) were effective inhibitors of hFAAH. Notably, compounds with 4-chlorobenzyl (19) and 4-fluorobenzyl (20) tails at the piperazine side were identified as the most active inhibitors with IC values of 0. Read More

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Design, synthesis, SAR, and biological evaluation of saccharin-based hybrids as carbonic anhydrase inhibitors.

Arch Pharm (Weinheim) 2022 Apr 28:e2200019. Epub 2022 Apr 28.

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.

Saccharin is a cyclic secondary sulfonamide, which is a selective inhibitor of the tumor-associated carbonic anhydrase (CA; EC 4.2.1. Read More

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The current scenario on anticancer activity of artemisinin metal complexes, hybrids, and dimers.

Arch Pharm (Weinheim) 2022 Apr 28:e2200086. Epub 2022 Apr 28.

Hubei Provincial Academy of Eco-Environmental Sciences, Wuhan, Hubei, People's Republic of China.

Cancer, the most significant cause of morbidity and mortality, has already posed a heavy burden on health care systems globally. In recent years, cancer treatment has made a significant breakthrough, but cancer cells inevitably acquire resistance, and the efficacy of the treatment is greatly reduced as the tumor progresses. To overcome the above issues, novel chemotherapeutics are needed urgently. Read More

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Safe and selective anticancer agents from tetrafluorinated azobenzene-imidazolium ionic liquids: Synthesis, characterization, and cytotoxic effects.

Arch Pharm (Weinheim) 2022 Apr 27:e2200085. Epub 2022 Apr 27.

School of Chemical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia.

A new series of tetrafluorinated azobenzene-imidazolium salts is reported. The azobenzene and imidazolium moieties were functionalized with long alkyl chains and connected via a methylene spacer of varying lengths (n = 3-12). They were characterized using FTIR and NMR spectroscopy, and elemental microanalysis. Read More

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2,2,2-Trifluoroethanol-mediated hydroarylation of fluorinated alkynes with indoles: Application to diindolylmethanes.

Arch Pharm (Weinheim) 2022 Apr 25:e2100488. Epub 2022 Apr 25.

Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Tübingen, Germany.

A new mild and practically simple alkyne hydroarylation protocol for the synthesis of 3-(indol-3-yl)-3-(trifluoromethyl)acrylic acid esters by the reaction of indole derivatives with ethyl/methyl 4,4,4-trifluoro-3-(indol-3-yl)but-2-enoates in trifluoroethanol was developed. This method has the following advantages: no catalyst, atom economy, high yields, broad substrate scope, and large-scale synthesis. The potential application of this protocol was further demonstrated by the synthesis of a variety of CF -substituted synthons and a new class of (un)symmetrical 3,3'-diindolylmethanes with a quaternary carbon core that might be biologically active. Read More

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Identification of 9H-purin-6-amine derivatives as novel aldose reductase inhibitors for the treatment of diabetic complications.

Arch Pharm (Weinheim) 2022 Apr 24:e2200043. Epub 2022 Apr 24.

Faculty of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Yancheng, China.

A series of 9H-purin-6-amine derivatives as aldose reductase (ALR) inhibitors were designed and synthesized. Most of these derivatives, having a C6-substituted benzylamine side chain and N9 carboxylic acid on the core structure, were found to be potent and selective ALR inhibitors, with submicromolar IC values against ALR2. Particularly, compound 4e was the most active with an IC value of 0. Read More

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A comprehensive review of recent advances in the biological activities of 1,2,4-oxadiazoles.

Authors:
Omnia M Hendawy

Arch Pharm (Weinheim) 2022 Apr 21:e2200045. Epub 2022 Apr 21.

Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf, Saudi Arabia.

Nitrogen heterocycles play an essential role in medication development. The 1,2,4-oxadiazole heterocycle has been extensively studied, yielding a large variety of molecules with varied biological functions. The 1,2,4-oxadiazole shows bioisosteric equivalency with ester and amide moieties. Read More

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New quinoxalin-2(1H)-one-derived VEGFR-2 inhibitors: Design, synthesis, in vitro anticancer evaluations, in silico ADMET, and docking studies.

Arch Pharm (Weinheim) 2022 Apr 18:e2200048. Epub 2022 Apr 18.

Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.

More than 70% of cancer patients who are treated with chemotherapeutics do not show a durable response. As part of the global plan seeking new effective chemotherapeutics, here, we report the synthesis and in vitro and computational studies of new lenvatinib and sorafenib analog quinoxalines as vascular endothelial growth factor receptor II (VEGFR-2) tyrosine kinase inhibitors. The central quinolone and pyridine moieties of the Food and Drug Administration-approved anticancer agents lenvatinib and sorafenib were replaced with the versatile quinoxaline scaffold that has been exploited for developing potent cytotoxic agents. Read More

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QSAR-driven synthesis of antiproliferative chalcones against SH-SY5Y cancer cells: Design, biological evaluation, and redesign.

Arch Pharm (Weinheim) 2022 Apr 18:e2200042. Epub 2022 Apr 18.

Escuela de Química y Farmacia, Facultad de Farmacia, Universidad de Valparaíso, Valparaíso, Chile.

Neuroblastoma is one of the most frequent types of cancer found in infants, and traditional chemotherapy has limited efficacy against this pathology. Thus, the development of new compounds with higher activity and selectivity than traditional drugs is a current challenge in medicinal chemistry research. In this study, we report the synthesis of 21 chalcones with antiproliferative activity and selectivity against the neuroblastoma cell line SH-SY5Y. Read More

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New pyrimidine/thiazole hybrids endowed with analgesic, anti-inflammatory, and lower cardiotoxic activities: Design, synthesis, and COX-2/sEH dual inhibition.

Arch Pharm (Weinheim) 2022 Apr 15:e2200024. Epub 2022 Apr 15.

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

Some cyclooxygenase (COX)-2 selective medications were withdrawn from the market just a few years after their production due to cardiovascular side effects. In this study, a new series of pyrimidine/thiazole hybrids 7a-p was synthesized as selective COX-2/soluble epoxide hydrolase (sEH) inhibitors with analgesic and anti-inflammatory effects, and lower cardiotoxicity effects. The target compounds were synthesized and in vitro tested against COX-1, COX-2, and sEH enzymes. Read More

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Cinnamic acid hybrids as anticancer agents: A mini-review.

Arch Pharm (Weinheim) 2022 Apr 14:e2200052. Epub 2022 Apr 14.

WuXi AppTec Co., Ltd., Shanghai, Peoples' Republic of China.

Cancer, as a long-lasting and dramatic disease, affects almost one-third of human beings globally. Chemotherapeutics play an important role in cancer treatment, but multidrug resistance and severe adverse effects have already become the main causes of failure in tumor chemotherapy. Therefore, it is an urgent need to develop novel chemotherapeutics. Read More

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Novel pyrazolo[3,4-b]pyridine derivatives: Synthesis, structure-activity relationship studies, and regulation of the AMPK/70S6K pathway.

Arch Pharm (Weinheim) 2022 Apr 12:e2100465. Epub 2022 Apr 12.

Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China.

A series of novel pyrazolo[3,4-b]pyridine derivatives were designed, synthesized, and biologically evaluated for anti-lung cancer activity. Structure-activity relationship and AutoGPA models were constructed based on the in vitro antiproliferative potency of the compounds against a human lung adenocarcinoma cell line (A549). Compound 9d exhibits improved potency for A549 cell growth inhibition (3. Read More

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Development of fluorinated nicotinonitriles and fused candidates as antimicrobial, antibiofilm, and enzyme inhibitors.

Arch Pharm (Weinheim) 2022 Apr 11:e2200040. Epub 2022 Apr 11.

Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

The antimicrobial assessments of two new series of nicotinonitriles and pyrido[2,3-d]pyrimidines were performed using amoxicillin and nystatin as reference standards. Outstanding antifungal activities were achieved by some target compounds; for instance, compounds 7 and 9 displayed a minimal inhibitory concentration (MIC) value of 1.95 µg/ml toward Candida albicans, compound 11 showed a potent anti-Rhizopus effect (MIC 1. Read More

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Cardioprotective effect of silymarin nanoemulsion on 5-fluorouracil-induced cardiotoxicity in rats.

Arch Pharm (Weinheim) 2022 Apr 11:e2200060. Epub 2022 Apr 11.

Cellular and Molecular Biology Research Center, Health Research Institute, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

5-Fluorouracil (5-FU)-associated cardiotoxicity has been ranked as the second most common cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. In the present study, we investigated the protective impacts of silymarin (SIL) and silymarin nanoemulsion (SLN) against cardiotoxicity caused by 5-FU in rats. Thirty male Wistar rats were divided into six groups as follows: control, SLN (5 mg/kg), SIL (5 mg/kg), 5-FU + SLN, 5-FU + SIL, and 5-FU. Read More

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Synthesis and antinociceptive activity of four 1H-isoindolo-1,3(2H)-diones.

Arch Pharm (Weinheim) 2022 Apr 9:e2100423. Epub 2022 Apr 9.

Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.

The present study aimed to design and synthesize a series of 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl phthalimide derivatives, which are analogs of 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives with proven analgesic effect. In accordance with the basic principle proposed by Lipinski's rule, the probable bioavailabilities of the F1-F4 phthalimides were assessed. The obtained values indicate good absorption after oral administration and the ability to cross the blood-brain barrier. Read More

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Design, synthesis, cytotoxicity, and molecular docking studies of novel thiazolyl-hydrazone derivatives as histone lysine acetyl-transferase inhibitors and apoptosis inducers.

Arch Pharm (Weinheim) 2022 Apr 8:e2200076. Epub 2022 Apr 8.

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

Compounds containing both thiazole and arylsulfone moieties are recognized for their high biological activity and ability to fight a variety of ailments. Thus, in this context, new derivatives of (thiazol-2-yl)hydrazone with an arylsulfone moiety were synthesized as CPTH2 analogs with potent anti-histone lysine acetyl-transferase activity. Compounds 3, 4, 10b, and 11b showed an excellent inhibitory effect on P300 (E1A-associated protein p300), compared to CPTH2. Read More

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The antimalarial activity of 1,2,4-trioxolane/trioxane hybrids and dimers: A review.

Arch Pharm (Weinheim) 2022 Apr 6:e2200077. Epub 2022 Apr 6.

College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, Jilin, China.

Malaria, a mosquito-borne parasitic infection caused by protozoan parasites belonging to the genus Plasmodium, is a dangerous disease that contributes to millions of hospital visits and hundreds and thousands of deaths across the world, especially in Sub-Saharan Africa. Antimalarial agents are vital for treating malaria and controlling transmission, and 1,2,4-trioxolane/trioxane-containing agents, especially artemisinin and its derivatives, own antimalarial efficacy and low toxicity with unique mechanisms of action. Moreover, artemisinin-based combination therapies were recommended by the World Health Organization as the first-line treatment for uncomplicated malaria infection and have remained as the mainstay of the treatment of malaria, demonstrating that 1,2,4-trioxolane/trioxane derivatives are useful prototypes for the control and eradication of malaria. Read More

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Chondroprotection of fruit peels in a monosodium iodoacetate-induced osteoarthritis rat model via downregulation of Col1A1.

Arch Pharm (Weinheim) 2022 Apr 6:e2200028. Epub 2022 Apr 6.

Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt.

The potential of the fruit peels of mango, orange, cantaloupe, and pomegranate in the treatment of osteoarthritis (OA) was evaluated in a rat model. Their metabolic profiles were characterized using ultrahigh-performance liquid chromatography (UPLC)-electrospray ionization-mass spectroscopy and 66 albino rats were intra-articularly injected with monosodium iodoacetate in the knee joints. The extracts were orally administered at doses of 200 and 400 mg/kg for 28 days. Read More

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