title

آنالیز برهمکنش های بین مولکولی در اُکسادیازول های 2و5-استخلافی در مقابل اهداف مرتبط با سرطان

علیخانی, رادین ، رزاقی اصل, نیما ، حسین زاده, زهرا ، رمضانی, علی (1396) آنالیز برهمکنش های بین مولکولی در اُکسادیازول های 2و5-استخلافی در مقابل اهداف مرتبط با سرطان. در: 21st Iranian Pharmacy Students Seminar, Mar 6-9 , 2018, Ahvaz - Iran.

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عنوان انگليسی

Analysis of intermolecular binding interactions for novel cytotoxic 2,5-disubstituted oxadiazoles versus cancer relevant targets

خلاصه انگلیسی

Introduction and background: Oxadiazole nucleus is a privileged structure in medicinal chemistry. In continuation to our interest in bioactive heterocycles, a few novel synthesized 1,3,4-oxadiazole derivatives were subjected to structure based modeling with the aim of elucidating intermolecular interactions into chemotherapeutic targets. Selected targets were previously demonstrated to be inhibited by 1,3,4-oxadiazoles. Quantitative and qualitative structure binding relationship analysis of docked oxadiazole derivatives proposed binding affinity/mode for cytotoxic oxadiazole molecules within diverse validated targets. Methods: Ligand-flexible docking studies were performed using the molecular docking software, AutoDock 4.2. To elucidate the interactions of selected targets with 1,3,4-oxadiazole molecules (1-17), all the related structures were docked into the active site of validated decuple receptors. Besides, AutoDock driven binding affinities (ΔGb, ki, and LE) were subjected to linear regression analysis with in vitro target inhibitory activities. Results: Structure–binding relationship (SBR) studies confirmed that chemical structures possessing chlorine and bromine atoms on 5-phenyl ring and N-benzyl moieties (4 and 17) exhibited superior binding modes/energies in the majority of studied targets. Amine & pyrrole NH, and N3 of oxadiazole ring were the most frequent atoms participated in H-bond interactions necessary for the enzyme inhibition. Moreover; linear regression analysis demonstrated that telomerase, epidermal growth factor (EGF), and BCL-2 were desirable targets with relatively acceptable affinity toward oxadiazoles on A549 cell line. Discussion and Conclusion: Multi-target oriented study revealed some insights into binding mode of novel cytotoxic oxadiazole derivatives. On the basis of obtained results, a general structure activity relationship (SAR) pattern for candidate 1,3,4-oxadiazoles were represented and a few novel structures were proposed and virtually validated as potential anticancer agents. Since the assessed macromolecular targets were previously proved to be blocked by 1,3,4-oxadiazoles, the results of this study might be useful in further design of more potent cytotoxic 1,3,4-oxadiazole derivatives.

نوع سند :موضوع کنفرانس یا کارگاه (پوستر )
زبان سند : انگلیسی
نویسنده اول :رادین علیخانی
نویسنده مسئول :نیما رزاقی اصل
نویسنده :زهرا حسین زاده
نویسنده :علی رمضانی
کلیدواژه ها (انگلیسی):Cancer; Target, Oxadiazole; Docking
موضوعات :QV فارماکولوژی > QV 744 شیمی دارویی
بخش های دانشگاهی :دانشکده داروسازی > بخش شیمی دارویی
کد شناسایی :9873
ارائه شده توسط : دکتر نیما رزاقی اصل
ارائه شده در تاریخ :13 اسفند 1396 05:44
آخرین تغییر :13 اسفند 1396 05:44

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