Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor

Çevik, Ulviye Acar; Çeli̇k, İsmail; Mella, Jaime; Mellado, Marco; Özkay, Yusuf; Kaplancıklı, Zafer Asım

doi:10.1021/acsomega.2c01497

Cited by 27 publications

(12 citation statements)

References 30 publications

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“…The Aromatase Substrate undergoes rapid photobleaching in aqueous solutions 32 . In our experience, the linear phase begins in the kinetic mode for 60 mins.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro Aromatase enzymatic assay ability of the test compound (ziprasidone) to inhibit aromatase enzyme was performed using a aromatase Inhibitor Screening Kit (Catalog #K984-100; Store at -20°C) which is a high-throughput uorescence-based assay kit enables reliable, rapid, characterization of drugs and other small molecules for compound-aromatase interaction with human aromatase 32 . The experimental protocol was followed according to the user manual.…”

Section: Annexin V/pi Assay Formentioning

confidence: 99%

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In-silico and in-vitro study reveals Ziprasidone as a potential aromatase inhibitor against breast carcinoma

Sahu

Ahmad

Imtiyaz

et al. 2023

Preprint

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Aromatase enzyme plays a fundamental role in the development of estrogen receptors and due to this functionality, the enzyme has gained significant attention as a therapeutic for reproductive disorders and cancer diseases. The aromatase inhibitors, currently in clinical use, have such serious side effects that it is crucial to find novel aromatase inhibitors with more selective, less toxic, and more effective drug potency. The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and to find a functional pocket in the target by docking and MD simulations. For assessing cellular and metabolic activities as indicators of cell viability and cytotoxicity, in-vitro studies were performed by using the colorimetric MTT assay. Aromatase activities were determined by a fluorometric method. Cell morphology was assessed by phase-contrast light microscopy. Flow cytometry and Annexin V-FITC/PI staining assay determined cell cycle distribution and apoptosis. This study reports that CHEMBL598797 (Ziprasidone) is the most promising compound that showed excellent aromatase inhibitory activity. By using better drug design methods and experimental studies, our study identified a novel compound that could be effective as a high-potential drug candidate against aromatase enzyme. We conclude that the compound ziprasidone effectively blocks the cell cycle at the G1-S phase and induces cancer cell death. Further, in-vivo studies are vital for developing ziprasidone as an anticancer agent. Lastly, our research outcomes based on the results of the in-silico experiments may pave the way for identifying effective drug candidates fortherapeutic use in breast cancer.

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“…The Aromatase Substrate undergoes rapid photobleaching in aqueous solutions 32 . In our experience, the linear phase begins in the kinetic mode for 60 mins.…”

Section: Discussionmentioning

confidence: 99%

Section: Annexin V/pi Assay Formentioning

confidence: 99%

In-silico and in-vitro study reveals Ziprasidone as a potential aromatase inhibitor against breast carcinoma

Sahu

Ahmad

Imtiyaz

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Additionally, molecular docking studies were conducted to detect their binding sites and types of interactions with aromatases. Compounds ( 130 ) and ( 131 ) were also investigated via molecular dynamic simulations for its possible binding mode to CYP19A1 and it was found that both derivatives had great potential as compared to others [ 124 ].…”

Section: Miscellaneous Anticancer Properties Of 134-oxadiazole Deriva...mentioning

confidence: 99%

An Understanding of Mechanism-Based Approaches for 1,3,4-Oxadiazole Scaffolds as Cytotoxic Agents and Enzyme Inhibitors

et al. 2023

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The world’s health system is plagued by cancer and a worldwide effort is underway to find new drugs to treat cancer. There has been a significant improvement in understanding the pathogenesis of cancer, but it remains one of the leading causes of death. The imperative 1,3,4-oxadiazole scaffold possesses a wide variety of biological activities, particularly for cancer treatment. In the development of novel 1,3,4-oxadiazole-based drugs, structural modifications are important to ensure high cytotoxicity towards malignant cells. These structural modification strategies have shown promising results when combined with outstanding oxadiazole scaffolds, which selectively interact with nucleic acids, enzymes, and globular proteins. A variety of mechanisms, such as the inhibition of growth factors, enzymes, and kinases, contribute to their antiproliferative effects. The activity of different 1,3,4-oxadiazole conjugates were tested on the different cell lines of different types of cancer. It is demonstrated that 1,3,4-oxadiazole hybridization with other anticancer pharmacophores have different mechanisms of action by targeting various enzymes (thymidylate synthase, HDAC, topoisomerase II, telomerase, thymidine phosphorylase) and many of the proteins that contribute to cancer cell proliferation. The focus of this review is to highlight the anticancer potential, molecular docking, and SAR studies of 1,3,4-oxadiazole derivatives by inhibiting specific cancer biological targets, such as inhibiting telomerase activity, HDAC, thymidylate synthase, and the thymidine phosphorylase enzyme. The purpose of this review is to summarize recent developments and discoveries in the field of anticancer drugs using 1,3,4-oxadiazoles.

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“…One of the principal strategies for drug discovery of new drug candidates is to amalgamate two or more pharmacophoric moieties in a single molecule to achieve the synergistic effect or obtain anticancer agents via a novel mechanism of action. In light of the afore-mentioned facts and continuation of our previous studies on identifying new antiproliferative activities, 16,23–26 hybrid compounds containing a 1,2,4-triazole ring and a hydrazone moiety were synthesized by employing an iodine mediated reaction in an attempt to get new effective anticancer molecules with increased potency (Fig. 3).…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, molecular docking and biological evaluation of 1,2,4-triazole derivatives possessing a hydrazone moiety as anti-breast cancer agents

Tapera,

Kekeçmuhammed,

Tunc

et al. 2023

New J. Chem.

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Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor

Cited by 27 publications

References 30 publications

In-silico and in-vitro study reveals Ziprasidone as a potential aromatase inhibitor against breast carcinoma

In-silico and in-vitro study reveals Ziprasidone as a potential aromatase inhibitor against breast carcinoma

An Understanding of Mechanism-Based Approaches for 1,3,4-Oxadiazole Scaffolds as Cytotoxic Agents and Enzyme Inhibitors

Design, synthesis, molecular docking and biological evaluation of 1,2,4-triazole derivatives possessing a hydrazone moiety as anti-breast cancer agents

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