Synthesis, photophysical, computational evaluation of pharmacokinetic properties and ADMET profile for novel compounds incorporating pyrazole and 1,3,4-oxadiazole moieties

IF 2.2 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2025-09-13 DOI:10.1016/j.tet.2025.134943

Rômulo Gabriel de Miranda de Paula Pinto , Maria Beatriz Póvoa Passos , Mariana Carvalho de Oliveira , Nayra Cordeiro da Conceição , Reinaldo Barros Geraldo , Leonardo Alves Miceli , Francislene Juliana Martins , Bernardo Almeida Iglesias , Mateus Henrique Köhler , Marcos Costa de Souza , Helena Carla Castro , Leandro Ferreira Pedrosa

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Abstract

Four molecular hybrids containing pyrazole and 1,3,4-oxadiazole nuclei were synthesized in five steps, yielding good results. Photophysical analysis by absorption and emission techniques are conducted and compounds reveal UV emission peaks. TDDFT calculations by NTO analysis shows the HOMO-LUMO plots of derivatives, with electronic contribution of entire molecule. Computational methods, including Lipinski's Rule of Five and Veber's Filter, confirmed favorable pharmacokinetic characteristics and enhanced bioavailability. Toxicity assessments classified all compounds under toxic category III, indicating noncarcinogenic and non-mutagenic properties. Molecular docking analysis revealed promising interactions against C. albicans, particularly with the RTT109 enzyme. Compound 7d showed the highest potential as an antifungal agent. The study underscores the importance of computational methods in early drug discovery, offering insights for lead compound selection and optimization, utilizing the cooperative characteristics of pyrazole and 1,3,4-oxadiazole nuclei.

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含吡唑和1,3,4-恶二唑的新型化合物的合成、光物理、药代动力学性质和ADMET谱的计算评价

以吡唑和1,3,4-恶二唑为核，分5步合成了4个杂化分子，取得了较好的效果。利用吸收和发射技术进行了光物理分析，化合物显示出紫外发射峰。NTO分析的TDDFT计算显示衍生物的HOMO-LUMO图，具有整个分子的电子贡献。计算方法，包括Lipinski's Rule of Five和Veber's Filter，证实了良好的药代动力学特性和增强的生物利用度。毒性评估将所有化合物归为毒性III类，表明其无致癌性和无致突变性。分子对接分析显示有希望与白色念珠菌相互作用，特别是与RTT109酶。化合物7d的抑菌潜力最大。该研究强调了计算方法在早期药物发现中的重要性，利用吡唑和1,3,4-恶二唑核的协同特性，为先导化合物的选择和优化提供了见解。

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.