Unraveling Structural and Anticancer Properties of Pyridine-Oxadiazole Derivatives: Single-Crystal XRD, Hirshfeld Analysis, and Cytotoxicity against A549 Cells.

IF 4.3 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

ACS Omega Pub Date : 2025-06-01 eCollection Date: 2025-06-10 DOI:10.1021/acsomega.5c02152

Yogeesha N Nayak, Deepika Dwarakanath, Keerthana Suresh Kizhakkanoodan, Rajeev K Sinha, K Sreedhara Ranganath Pai, Bharath Raja Guru, Santosh L Gaonkar

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引用次数: 0

Abstract

A new series of pyridine-based 1,3,4-oxadiazole derivatives was synthesized and structurally characterized using FTIR, NMR, HRMS, and single-crystal X-ray diffraction. Hirshfeld surface analysis of the meta-methyl-substituted derivative revealed key intermolecular interactions. Cytotoxicity was evaluated against A549 lung cancer cells via MTT assay, where compound 5k (3,5-dichloro substitution) showed the highest activity (IC₅₀ = 6.99 ± 3.15 μM), comparable to 5-fluorouracil. Structure-activity relationship analysis indicated that meta-substituents enhance activity, while bulky or strongly electron-withdrawing groups reduce it. In silico studies demonstrated favorable ADME properties, and molecular docking with CDK2 revealed strong binding affinities. Molecular dynamics simulations confirmed the stability of the 5k-CDK2 complex over 100 ns. These findings suggest that pyridine-oxadiazole hybrids, particularly 5k, are promising candidates for further development as anticancer agents.

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吡啶-恶二唑衍生物的结构和抗癌性质：单晶XRD， Hirshfeld分析和对A549细胞的细胞毒性。

合成了一系列新的吡啶基1,3,4-恶二唑衍生物，并利用FTIR、NMR、HRMS和单晶x射线衍射对其进行了结构表征。间甲基取代衍生物的Hirshfeld表面分析揭示了关键的分子间相互作用。MTT法测定了化合物5k（3,5-二氯取代）对A549肺癌细胞的细胞毒性，IC50值为6.99±3.15 μM，与5-氟尿嘧啶相当。构效关系分析表明，间取代基提高了活性，而大体积或强吸电子基团降低了活性。硅研究显示了良好的ADME特性，与CDK2的分子对接显示出很强的结合亲和力。分子动力学模拟证实了5k-CDK2复合物在100 ns内的稳定性。这些发现表明，吡啶-恶二唑复合物，特别是5k，是进一步开发抗癌药物的有希望的候选者。

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来源期刊

ACS Omega Chemical Engineering-General Chemical Engineering

CiteScore

6.60

自引率

4.90%

发文量

3945

审稿时长

2.4 months

期刊介绍： ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.