Publications by authors named "Sussan Kabudanian Ardestani"

25 Publications

  • Page 1 of 1

Increased expression of endoplasmic reticulum stress-related caspase-12 and CHOP in the hippocampus of EAE mice.

Brain Res Bull 2019 04 6;147:174-182. Epub 2019 Feb 6.

Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The role of endoplasmic reticulum (ER) stress has been proposed in several neurodegenerative and autoimmune diseases and may contribute to neural apoptosis. The complex role of ER stress-mediated apoptosis introduces a novel angle on multiple sclerosis (MS) research. Nevertheless, the mechanisms through which ER stress intermediates apoptosis are not entirely understood. To this aim, we examined the expression of C/EBP homologous protein (CHOP), caspase-12, and protein disulfide isomerase (PDI) in mice with experimental autoimmune encephalomyelitis (EAE). We found the upregulated expression of CHOP, caspase-12, and PDI in the brain of EAE mice in comparison to healthy mice. Furthermore, immunofluorescent dual-label staining verified elevated levels of caspase-12/CHOP in astrocytes, oligodendrocytes, and microglia in the hippocampus section of EAE mice. This study highlighted the presence of ER stress and increased activation of caspase-12 in the hippocampus of mice in response to EAE induction. Higher levels of caspase-12/CHOP in hippocampal oligodendrocytes as compared with microglia and astrocytes denote that oligodendrocytes are particularly sensitive to ER-mediated apoptosis. In conclusion, the regulation of ER stress pathway would be beneficial for the survival of oligodendrocyte.
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http://dx.doi.org/10.1016/j.brainresbull.2019.01.020DOI Listing
April 2019

Novel quinazolin-4(3H)-one linked to 1,2,3-triazoles: Synthesis and anticancer activity.

Chem Biol Drug Des 2018 07 18;92(1):1373-1381. Epub 2018 May 18.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

In this work, a wide range of novel quinazolin-4(3H)-one linked to 1,2,3-triazoles was designed, synthesized, and evaluated against a panel of three human breast (MDA-MB-231, MCF-7, T-47D), lung (A549), and prostate (PC3) cancer cell lines. Our results revealed that the anticancer activity of the synthesized compounds was selectively affected by the presence of methoxy group on the linker between quinazolinone and 1,2,3-triazole moieties. According to the calculated IC values, compounds 6q, 6w, and 6x showed good cytotoxicity against breast cancer cell lines even more effective than the reference drug, etoposide. Compounds 6q and 6u were found to be potent compounds against A549, non-small-cell lung cancer (NSCLC), comparing with erlotinib. Also, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that potent compounds induced apoptosis in human cancer cell lines. Molecular docking studies were performed to clarify the inhibition mode of compounds 6g, 6u, 6w, and 6x over the EGFR active site. The most promising compounds, 6q and 6u, possessing 3-methoxy group were well oriented to the gatekeeper hydrophobic pocket of EGFR active site and interact well with Ala719, Val702, and Leu820 through hydrophobic interaction.
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http://dx.doi.org/10.1111/cbdd.13203DOI Listing
July 2018

Caspase-dependent apoptosis induced by two synthetic halogenated flavanones, 3',7-dichloroflavanone and 3',6-dichloroflavanone, on human breast and prostate cancer cells.

In Vitro Cell Dev Biol Anim 2018 Feb 20;54(2):136-146. Epub 2017 Dec 20.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The destruction of cancer cells with chemotherapeutic agents is normally achieved through apoptosis. We previously introduced two synthetic halogenated flavanone derivatives, 3,7-dichloroflavanone (3'-7 DCF) and 3,6-dichloroflavanone (3'-6 DCF), as potential apoptosis-inducing agents. In the current study, we investigated the ability of these compounds in triggering intrinsic or/and extrinsic pathway of apoptosis in breast and prostate cancer cells. Also, the synergistic effect of 3'-7 DCF with TLR3 (Toll-like receptor 3) agonist in apoptosis induction was evaluated on PC3 and LNCaP human prostate cancer cells. The involved pathway of apoptosis in the treated cells was delineated by caspase-3 activity assay, PARP-1 (poly(ADP-ribose)polymerase-1) cleavage, and procaspase-9 cleavage as markers of the intrinsic pathway and procaspase-8 cleavage as the marker of the extrinsic pathway. With the exception of the normal cells, treatment of all cell lines with both 3'-7 DCF and 3'-6 DCF triggered the cleavage of procaspase-8 and procaspase-9. These results indicate that the intrinsic and the extrinsic pathways of apoptosis are the mechanisms of the toxicity of flavanones in these cancer cell lines. However, the cytoxicity of the compound 3'-7 DCF was not synergistic with TLR3 agonist. Interestingly, the activation of caspases-9 preceeded that of caspase-8 suggesting that the intrinsic pathway is the primary reason for apoptosis induction by the flavanones.
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http://dx.doi.org/10.1007/s11626-017-0209-3DOI Listing
February 2018

Synthesis and Leishmanicidal Activity of 1-[5-(5-Nitrofuran-2-yl)-1, 3, 4-Thiadiazole-2-yl]-4-BenzoylePiperazines.

Iran J Pharm Res 2017 ;16(3):904-909

Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

A series of 5-nitrofuran-2-yl)-1, 3, 4-thiadiazole-2-yl derivatives 6a-6e have been synthesized and screened for anti-leishmanial activity against the promastigote form of . The structure of Schiff bases were confirmed by H NMR, IR. Screening results indicate that all of the designed and synthesized final compounds (6a-6e) significantly reduced the viability of promastigotes of in comparison toglucantime (IC 3× 10 μg/mL). Meta and Para substitutions in benzene ring containing compounds were more potent than other derivative and the most potent compounds were 6d, 6e with IC value 94 µm and 77.6 µm, respectively. The experimental data proposes that 5-nitrofuran-2-yl)-1, 3, 4-thiadiazole-2-yl derivatives may be further investigated as a candidate drug for treatment of cutaneous leishmaniasis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610746PMC
January 2017

Correlation between MMP-9 and MMP-9/ TIMPs Complex with Pulmonary Function in Sulfur Mustard Exposed Civilians: Sardasht-Iran Cohort Study.

Arch Iran Med 2017 Feb;20(2):74-82

Immunoregulation Research Center, Shahed University, Tehran, I.R. Iran.

Background: Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues. The aim of this study was assessing the possible role of MMP-9 and TIMPs in SM-induced lung symptoms and signs in exposed patients 20 years after exposure.

Methods: Totally, 372 male volunteers with a history of SM- exposure and 128 age- and sex-matched unexposed controls participated and were divided into three groups: normal, mild and moderate-severe. All participants underwent clinical evaluation and pulmonary function tests and serum concentrations of MMP-9 and its inhibitors were measured using the ELISA technique.

Results: Serum level of MMP-9 was increased in the SM exposed group who had moderate-severe pulmonary complications compared with the SM exposed with normal lung (2.321 ± 2.836 vs. 1.546 ± 2.176, P = 0.001) while only the MMP-9/TIMP-4 complex was elevated in the SM exposed with normal lung individuals compared to its corresponding control group (85 ± 265 vs. 82 ± 222, P = 0.025). Although MMP-9 and its inhibitors did not show any correlation with spirometry findings, elevated circulating MMP-9 was detected in SM exposed patients with chronic chough and hemoptysis (P = 0.013 and P = 0.013 respectively).

Conclusion: High level of tissue disruption and remodeling mediators could influence lung structure in long-term after SM-exposure. The correlation of clinical evaluation with these factors efficiently helps us to identify important effectors.
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http://dx.doi.org/0172002/AIM.003DOI Listing
February 2017

Synthesis and biological evaluation of novel imidazopyrimidin-3-amines as anticancer agents.

Chem Biol Drug Des 2017 05 29;89(5):797-805. Epub 2016 Dec 29.

Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Groebke-Blackburn-Bienayme reaction has been utilized for the synthesis of new imidazo[1,2-a]pyrimidine derivatives as novel anticancer agents. The cytotoxic activities of compounds were evaluated against human cancer cell lines including MCF-7, T-47D, and MDA-MB-231, compared with etoposide as the standard drug. Among the tested compounds, hydroxy- and/or methoxy-phenyl derivatives (6a-c and 6k) with IC values of 6.72-14.36 μm were more potent than etoposide against all cell lines. The acridine orange/ethidium bromide double staining and DNA fragmentation studies demonstrated that the cytotoxic effect of 3-hydroxy-4-methoxyphenyl derivative 6c is associated with apoptosis in cancer cells.
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http://dx.doi.org/10.1111/cbdd.12904DOI Listing
May 2017

Anticancer effects of synthetic hexahydrobenzo [g]chromen-4-one derivatives on human breast cancer cell lines.

Breast Cancer 2017 Mar 1;24(2):299-311. Epub 2016 Jun 1.

Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Cancer results from a series of molecular changes that alter the normal function of cells. Breast cancer is the second leading cause of cancer death in women. To develop novel anticancer agents, new series of chromen derivatives were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines.

Method: The growth inhibitory activities of synthesized hexahydrobenzo chromen-4-one were screened against six human cancer cell lines using an in vitro cell culture system (MTT assay). Fluorochrome staining (acridine orange/ethidium bromide double staining) and DNA fragmentation by the diphenylamine method were used to investigate the effects of most potent compounds on the process of apoptosis in breast cancer cell lines. To determine the mechanism of apoptosis, ROS and NOX production in treated breast cancer cells with compounds was evaluated.

Results: The cytotoxicity data of tested compounds demonstrate these compounds had varying degree of toxicity. Compound 7h was the most potent compound with IC = 1.8 ± 0.6 µg/mL against T-47D cell line. Analyses of the compounds treated (MCF-7, MDA-MB-231, and T-47D) cells by acridine orange/ethidium bromide double staining and DNA fragmentation by the diphenylamine method showed that the synthetic compounds induce apoptosis in the cells. A significant increase in ROS production was observed in T-47D cells treated with IC value of compound 7g. Incubation with IC value of synthetic compounds increased the NOX production in cell lines, especially T-47D cells.

Conclusion: Our results show that most compounds have a significant anti-proliferative activity against six human cancer cell lines. The observations confirm that chromen derivatives have induced the cell death through apoptosis.
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http://dx.doi.org/10.1007/s12282-016-0704-5DOI Listing
March 2017

Novel N-2-(Furyl)-2-(chlorobenzyloxyimino) Ethyl Piperazinyl Quinolones: Synthesis, Cytotoxic Evaluation and Structure-Activity Relationship.

Iran J Pharm Res 2015 ;14(4):1095-103

Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. ; Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Quinolone antibacterials are one of the most important classes of pharmacological agents known as potent inhibitors of bacterial DNA gyrase and topoisomerase IV that efficiently inhibit DNA replication and transcription by generating several double-stranded DNA break. Some quinolone derivatives demonstrated inhibitory potential against eukaryote topoismarase II and substantial dose-dependent cytotoxic potential against some cancerous cells. In present study, synthesis and cytotoxic activity evaluation of new series of N-pipearzinyl quinolones containing N-2-(furyl-2 or 3-yl)-2-(chlorobenzyloxyimino) ethyl moiety 7a-i have been studied. Reaction of quinolone, with 2-bromo-1-(furan-2 or 3-yl)ethanone-O-substituted chlorobenzyloxime in DMF in presence of NaHCO3 at room temperature, gave the title compounds N-2-(furan-2 or 3-yl)-2-(chlorobenzyloxyiminoethyl) quinolone 7a-i. Synthesized compounds were further evaluated in-vitro against three human breast tumor cell lines. Preliminary screening indicated that compound 7 g demonstrated significant growth inhibitory potential against all evaluated cell lines. The results of structure-activity relationship study exhibited that quinolone derivatives are superior in cytotoxic potential compared to 1, 8-naphthyridone series. Furthermore, ethyl quinolone derivatives were more potent cytotoxic agents comparing with cyclopropyl quinolones.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673937PMC
December 2015

Design, synthesis, in vitro cytotoxic activity evaluation, and apoptosis-induction study of new 9(10H)-acridinone-1,2,3-triazoles.

Mol Divers 2015 Nov 14;19(4):787-95. Epub 2015 Jul 14.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

A new series of 9(10H)-acridinone-1,2,3-triazole derivatives were designed, synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines. The acridone skeleton was prepared through the Ullman condensation of 2-bromobenzoic acid and anilines. Subsequently, it was functionalized with propargyl bromide. Then, a click reaction of the latter compound and in situ prepared 1-(azidomethyl)-4-methoxybenzene derivatives led to the formation of the desired triazole products. Finally, all products were investigated for their capability to cause cytotoxicity against MCF-7, T-47D, and MDA-MB-231 cell lines. Among them, 2-methoxy-10-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H)-one 8c exhibited the most potency [Formula: see text] against MCF-7 cells, being more potent than etoposide [Formula: see text]. Also, apoptosis induced by compound 8c was confirmed via acridine orange/ethidium bromide and Annexin V-FITC/propidium iodide (PI) double staining.
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http://dx.doi.org/10.1007/s11030-015-9616-0DOI Listing
November 2015

Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing trans-stilbene scaffold.

Eur J Med Chem 2015 May 26;95:492-9. Epub 2015 Mar 26.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran. Electronic address:

A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were designed, synthesized, and evaluated against human breast cancer cell lines including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl derivative 7h showed the best profile of activity (IC50 < 5 μM) against all cell lines, being 2-fold more potent than standard drug, etoposide. Our investigation revealed that the cytotoxic activity was significantly affected by N3-alkyl substituents. Furthermore, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that the prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells.
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http://dx.doi.org/10.1016/j.ejmech.2015.03.057DOI Listing
May 2015

Cytotoxic and apoptotic effects of synthetic benzochromene derivatives on human cancer cell lines.

Naunyn Schmiedebergs Arch Pharmacol 2014 Dec 27;387(12):1199-208. Epub 2014 Sep 27.

Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

With the aim of discovering potential cytotoxic agents, a series of benzochromene derivatives were screened for their cytotoxic activity against seven human cancer cell lines by standard 3-(4, 5-dimethyl thiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis, as the mechanism of cell death, was investigated morphologically by acridine orange/ethidium bromide staining and cell surface expression assay of phosphatidylserine by Annexin V-PE/7-AAD technique. The effects of compounds on reactive oxygen species (ROS) and nitric oxide (NO) generations in three human breast cancer cell lines were also studied. All compounds showed significant cytotoxic activity with inhibitory concentration (IC50) values in the micromolar range (4.6-21.5 μM). The results of apoptosis evaluation suggested that the cytotoxic activity of these compounds in breast cancer cells occurs via apoptosis. MCF-7 cell line showed higher levels of ROS and NO production after treatment with compounds. The increase in ROS production after 4 and 24 h indicated that one of the ways that these compounds can induce apoptosis is by increasing ROS generation. Cytotoxic and apoptotic effects of these compounds in human cancer cells indicated that they can be a good candidate for further pharmacological studies to discover effective anticancer agents.
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http://dx.doi.org/10.1007/s00210-014-1038-5DOI Listing
December 2014

Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents.

Eur J Med Chem 2014 Oct 6;86:562-9. Epub 2014 Sep 6.

Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A series of 2-aryl-3-nitro-2H-chromenes 4a-u were designed as hybrid analogs of flavanone, β-nitrostyrene and nitrovinylstilbene scaffolds. They were synthesized from the reaction of appropriate β-nitrostyrenes and salicylaldehydes in good yields. In vitro cytotoxic activities of compounds 4a-u were tested against breast cancer cell lines including MCF-7, T-47D and MDA-MB-231. Most compounds exhibited good cytotoxic activity against selected cell lines, being more potent than standard drug etoposide. Representatively, 8-methoxy-3-nitro-2-(4-chlorophenyl)-2H-chromene (4l) with IC50 = 0.2 μM against MCF-7 cells, was 36-times more potent than etoposide. Apoptosis as a mechanism of cell death for selected compounds 4h and 4l was confirmed morphologically by acridine orange/ethidium bromide double staining and TUNEL analysis, as well as caspase-3 activation assay.
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http://dx.doi.org/10.1016/j.ejmech.2014.09.017DOI Listing
October 2014

Synthesis and cytotoxic evaluation of some new[1,3]dioxolo[4,5-g]chromen-8-one derivatives.

Daru 2014 May 2;22:41. Epub 2014 May 2.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Homoisoflavonoids are naturally occurring compounds belong to flavonoid classes possessing various biological properties such as cytotoxicity. In this work, an efficient strategy for the synthesis of novel homoisoflavonoids, [1,3]dioxolo[4,5-g]chromen-8-ones, was developed and all compounds were evaluated for their cytotoxic activities on three breast cancer cell lines.

Methods: Our synthetic route started from benzo[d][1,3]dioxol-5-ol which was reacted with 3-bromopropanoic acid followed by the reaction of oxalyl chloride to afford 6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one. The aldol condensation of the later compound with aromatic aldehydes led to the formation of the title compounds. Five novel derivatives 4a-e were tested for their cytotoxic activity against three human breast cancer cell lines including MCF-7, T47D, and MDA-MB-231 using the MTT assay.

Results: Among the synthesized compounds, 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) exhibited the highest activity against three cell lines. Also the analysis of acridine orange/ethidium bromide staining results revealed that 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) and 7-(2-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4b) induced apoptosis in T47D cell line.

Conclusion: Finally, the effect of methoxy group on the cytotoxicity of compounds 4b-4d was investigated in and it was revealed that it did not improve the activity of [1,3]dioxolo[4,5-g]chromen-8-ones against MCF-7, T47D, and MDA-MB-231.
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http://dx.doi.org/10.1186/2008-2231-22-41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019946PMC
May 2014

2-Amino-4-(nitroalkyl)-4H-chromene-3-carbonitriles as New Cytotoxic Agents.

Iran J Pharm Res 2013 ;12(4):679-85

Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. ; Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

A series of 2-amino-4-(nitroalkyl)-4H-chromene-3-carbonitriles were synthesized by an efficient multicomponent reaction in aqueous media using DBU as a catalyst at room temperature. Mild condition, environment friendly procedure and excellent yields are the main advantages of this procedure. The cytotoxic activity of target compounds were evaluated against three cancer cell lines MDA-MB-231, MCF-7 and T47D in comparison with etoposide as reference drug. Generally, all compounds showed good cell growth inhibitory activity with IC(50) values less than 30 μg/mL. Their activities were comparable or more potent than standard drug etoposide. The 6-bromo- derivatives 7e and 7f showed promising cytotoxic activity with IC50 values in the range of 3.46-18.76 μg/mL, being more potent than etoposide against all tested cell lines.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920703PMC
February 2014

Synthesis and in vitro cytotoxic activity of novel chalcone-like agents.

Iran J Basic Med Sci 2013 Nov;16(11):1155-62

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Objective(s): Chalcones and their rigid analogues represent an important class of small molecules having anticancer activities. Therefore, in this study the synthesis and cytotoxic activity of new 3-benzylidenchroman-4-ones were described as rigid chalcone analogues.

Materials And Methods: The reaction of resorcinol with 3-chloropropionic acid in the presence of CF3SO3H was afforded corresponding propiophenone. It was cyclized using 2M NaOH to give 7-hydroxy-4-chromanone. O-Alkylation of 7-hydroxy-4-chromanone with alkyl iodide in the presence of K2CO3 gave 7-alkoxychroman-4-one. Finally, condensation of chroman-4-one derivatives with different aldehydes afforded target compounds in good yields. The newly synthesized compounds were tested in vitro against different human cancer cell lines including K562 (human erythroleukemia), MDA-MB-231 (human breast cancer), and SK-N-MC (human neuroblastoma) cells. The cell viability was evaluated using MTT colorimetric assay.

Results: Most of the compounds showed good inhibitory activity against cancer cells. Among them, compound 4a containing 7-hydroxy group on chromanone ring and 3-bromo-4-hydroxy-5-methoxy substitution pattern on benzylidene moiety was the most potent compound with IC50 values ≤ 3.86 µg/ml. It was 6-17 times more potent than etoposide against tested cell lines.

Conclusion: We described synthesis and cytotoxic activity of poly-functionalized 3-benzylidenechroman-4-ones as new chalcone-like agents. These compounds can be considered as conformationally constrained congeners of chalcones to tolerate the poly-functionalization on the core structures for further optimization.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909627PMC
November 2013

Synthesis and evaluation of antiproliferative activity of substituted N-(9-oxo--xanthen-4-yl)benzenesulfonamides.

Tetrahedron Lett 2014 Jan;55(2):373-375

Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Several novel -(9-oxo--xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-(9-oxo--xanthen-4-yl)benzenesulfonamide showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives and exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDA-MB-468) cells. Structure-activity relationship studies revealed that xanthone benzenesulfonamide hybrid compounds can be used for development of new lead anticancer agents.
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http://dx.doi.org/10.1016/j.tetlet.2013.11.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895536PMC
January 2014

Synthesis and biological evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones as combretastatin analogs.

Eur J Med Chem 2013 25;70:692-702. Epub 2013 Oct 25.

Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

A series of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones 5 were designed as new heterocyclic analogs of combretastatin A-4 (CA-4). Indeed, the olefinic core structure of CA-4 has been replaced by 2(3H)-thiazole thione. The general synthetic strategy to prepare compounds 5 was based on the cyclocondensation reaction between triethylammonium N-(trimethoxyphenyl)dithiocarbamate and appropriate phenacyl halide. The cytotoxic activity evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones 5 against human cancer cell lines T47D, MCF-7 and MDA-MB-231 demonstrated that 4-methyl analog 5f showed the highest activity against all cell lines. Compound 5f had no significant toxicity towards non-tumoral cells MRC-5 and its cytotoxicity was apparently selective for cancer cells. The results of bioassays showed that the representative compound 5f depolymerized tubulin, inhibited cell proliferation, and induced apoptosis in cancer cells.
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http://dx.doi.org/10.1016/j.ejmech.2013.10.046DOI Listing
September 2014

Synthesis and In vitro cytotoxic activity evaluation of (E)-16-(substituted benzylidene) derivatives of dehydroepiandrosterone.

Daru 2013 May 1;21(1):34. Epub 2013 May 1.

Department of Medicinal Chemistry, Faculty of Pharmacy & Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background And The Purpose Of The Study: Modified androsterone derivatives are class of steroidal compounds with potential anticancer properties. Various steroidal derivatives containing substitution at position 16 have shown diversified pharmacological activities. In the present study, a new series of cytotoxic 16-(substituted benzylidene) derivatives of dehydroepiandrosterone (DHEA) were synthesized and evaluated against three different cancer cell lines.

Methods: The cytotoxic 16-(substituted benzylidene) derivatives of DHEA were synthesized via aldol condensation of DHEA with corresponding benzaldehyde derivatives. The cytotoxic activity of synthesized derivatives was evaluated against three different cancer cells including KB, T47D and SK-N-MC cell lines by MTT reduction colorimetric assay.

Results: The results indicated that 16-(substituted benzylidene) derivatives of DHEA could be served as a potent anti-cancer agent. The 3-cholro benzylidene derivatives of DHEA was the most potent synthesized derivative especially against KB and T47D cell lines (IC50 values were 0.6 and 1.7 μM; respectively).

Conclusion: The cytotoxic potential of novel benzylidene derivatives of DHEA is mainly attributed to the position and nature of the substituted group on the benzylidene pendant.
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http://dx.doi.org/10.1186/2008-2231-21-34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673839PMC
May 2013

Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives.

Daru 2013 Apr 12;21(1):31. Epub 2013 Apr 12.

Background And The Purpose Of The Study: There has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines.

Methods: The title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay.

Results: Although the direct analog of SJ-172550 (compound 5d) did not show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog 5c showed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound 5c resulted in the 3-chloro-4,5-dimethoxybenzylidene derivative 5b which demonstrated better cytotoxic profile against all tested cell lines (IC50 values = 7.56-25.04 μg/ml).

Conclusion: The results demonstrated that the cytotoxic activity of compound 5b against MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound 5b prototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.
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http://dx.doi.org/10.1186/2008-2231-21-31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668990PMC
April 2013

Cytotoxic activity evaluation and QSAR study of chromene-based chalcones.

Arch Pharm Res 2012 Dec 21;35(12):2117-25. Epub 2012 Dec 21.

Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Chalcone and chromene motifs are synthetic or naturally occurring scaffolds with significant cytotoxic profile. Two types of novel regioisomeric chromene-chalcone hybrids, namely 1-(6-chloro or 6-methoxy-2H-chromen-3-yl)-3-phenylprop-2-en-1-one (Type A) and 3-(6-chloro or 6-methoxy-2H-chromen-3-yl)-1-phenylprop-2-en-1-one (Type B), both with different substituents on the phenyl ring attached to propenone linkage, have been evaluated for their cytotoxic activity against breast cancer cell lines (MCF-7 and MDA-MB-231). The results indicate that type A of chromene-chalcones demonstrated better cytotoxic profile than type B especially in MDA-MB-231 cell line. In addition, the growth inhibitory activity of most of the target compounds is higher than Etoposide as a reference drug. QSAR analysis of these novel compounds demonstrated that topological and geometrical parameters are among the important descriptors that influence the cytotoxic activity profile of compounds.
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http://dx.doi.org/10.1007/s12272-012-1208-2DOI Listing
December 2012

Halogenated flavanones as potential apoptosis-inducing agents: synthesis and biological activity evaluation.

Eur J Med Chem 2012 Dec 2;58:573-80. Epub 2012 Nov 2.

Institute of Biochemistry and Biophysics, University of Tehran, PO Box 13145-1384, Tehran, Iran.

A series of halogenated flavanones were synthesized from 2-hydroxychalcones and tested for their cytotoxicity against a panel of human cancer cell lines. Among the synthesized compounds, 3',7-dichloroflavanone (2d) showed the highest activity against MCF-7, LNCaP, PC3, Hep-G2, KB and SK-N-MC cells. However, 3',6-dichloroflavanone (2g) with IC(50) value of 2.9 ± 0.9 μM was the most potent compound against MDA-MB-231 cells, being approximately 12 times more active than etoposide as reference drug. According to the flow-cytometric analysis, compound 2g can induce apoptosis by 66.19 and 21.37% in PC3 and MDA-MB-231 cells, respectively. The results of acridine orange/ethidium bromide staining and TUNEL assay suggested that the cytotoxic activity of this compound in PC3 and MDA-MB-231 cells occurs via apoptosis.
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http://dx.doi.org/10.1016/j.ejmech.2012.10.043DOI Listing
December 2012

New 5-(nitroheteroaryl)-1,3,4-thiadiazols containing acyclic amines at C-2: synthesis and SAR study for their antileishmanial activity.

J Enzyme Inhib Med Chem 2013 Aug 31;28(4):843-52. Epub 2012 May 31.

Department of Medicinal Chemistry, School of Pharmacy and Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

A novel series of 5-(5-nitrofuran-2-yl)-and 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole-2-amines bearing acyclic amine at C-2 position of thiadiazole ring were synthesized and evaluated in vitro against promastigote and amastigote forms of Leishmania major. The structure-activity of series was investigated by studying 40 compounds. The most active derivatives were hydroxypropylamino- and methoxypropylamino- analogs of 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole (compounds 29 and 32, respectively) with highest selectivity index (SI >12).
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http://dx.doi.org/10.3109/14756366.2012.689297DOI Listing
August 2013

2-Amino-3-cyano-4-(5-arylisoxazol-3-yl)-4H-chromenes: synthesis and in vitro cytotoxic activity.

Arch Pharm (Weinheim) 2012 May 20;345(5):386-92. Epub 2012 Jan 20.

Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

A new series of 4-aryl-4H-chromenes bearing a 5-arylisoxazol-3-yl moiety at the C-4 position were prepared as potential anticancer agents. The in vitro cytotoxic activity of the synthesized compounds was investigated against a panel of tumor cell lines including MCF-7 (breast cancer), KB (nasopharyngeal epidermoid carcinoma), Hep-G2 (liver carcinoma), MDA-MB-231 (breast cancer), and SKNMC (human neuroblastoma) using the MTT colorimetric assay. Doxorubicin, a well-known anticancer drug, was used as positive standard drug. Among the synthesized compounds, the 5-(3-methylphenyl)isoxazol-3-yl analog (7j) showed the most potent cytotoxic activity against all five human tumor cell lines.
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http://dx.doi.org/10.1002/ardp.201100345DOI Listing
May 2012

Synthesis and antileishmanial activity of novel 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituents.

Eur J Med Chem 2011 Jun 31;46(6):2602-8. Epub 2011 Mar 31.

Department of Medicinal Chemistry, School of Pharmacy and Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

In order to optimize the antileishmanial activity of piperazinyl-linked 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazoles, we synthesized a series of 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituent as scaffold found in pentamidine related antiprotozoals. The structure of target compounds was confirmed by IR, 1H NMR, 13C NMR and Mass spectral data. All compounds were tested for in vitro activity against the promastigote and amastigote forms of Leishmania major. From the results, we found that the substitution on amidine nitrogen has profound role in the biological activity of these compounds. The 5-nitrofuran-2-yl-1,3,4-thiadiazoles having n-propyl, n-butyl and benzyl side chain on benzamidine (as in compounds 2d, 2e and 2g, respectively) showed very good activity in both forms of promastigote and amastigote. The most active compound was N-propyl-4-(4-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-yl)piperazin-1-yl) benzamidine hydrochloride (2d) with IC50 value of 0.08 μM in promastigote model. This compound showed a very low level of toxicity against macrophages (CC50=785 μM), with the highest selectivity index (SI=78.5) among the tested compounds.
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http://dx.doi.org/10.1016/j.ejmech.2011.03.053DOI Listing
June 2011

Nitroimidazolyl-1,3,4-thiadiazole-based anti-leishmanial agents: synthesis and in vitro biological evaluation.

Eur J Med Chem 2009 Apr 9;44(4):1758-62. Epub 2008 Apr 9.

Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, P.O. Box 13145-1384, Tehran, Iran.

A series of 1-[5-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazol-2-yl]-4-aroylpiperazines were synthesized and evaluated in vitro against Leishmania major. Most of the target compounds exhibited good anti-leishmanial activity against the promastigote form of L. major at non-cytotoxic concentrations. The most active compound was 1-[(5-chloro-2-thienyl)carbonyl]-4-[5-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazol-2-yl]piperazine (5f) with an IC(50) value of 9.35+/-0.67 microM against L. major promastigotes. In addition, this compound was effective against intracellular L. major and significantly decreased the infectivity index.
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http://dx.doi.org/10.1016/j.ejmech.2008.03.039DOI Listing
April 2009