A review on pyrimidine-based pharmacophore as a template for the development of hybrid drugs with anticancer potential.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2025-02-12 DOI:10.1007/s11030-025-11112-x

Shivam Sharma, M Arockia Babu, Roshan Kumar, Thakur Gurjeet Singh, Ashish Ranjan Dwivedi, Gazanfar Ahmad, Kapil Kumar Goel, Bhupinder Kumar

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Abstract

The low efficacy and toxicity of traditional chemotherapy, led by drug resistance of targeted anticancer therapies, have mandated the exploration and development of anticancer molecules. In this league, hybrid drugs, owing to their peculiar multitargeted functionality and structural diversity, could serve as vital leads in this quest for drug discovery. They are plausibly found to offer added advantages considering the improved efficacy, low toxicity, and improved patient compliance. Among numerous heterocycles explored, pyrimidine derivatives epitomize as a valuable resource for the hybrid drug development due to their validated efficacy and versatility. The present review discusses the role of pyrimidine, a diversified pharmacophore in drug development and concepts of hybrid drugs. The study covers the recent advancements in pyrimidine-based hybrid pharmacophores. It delves further into the challenges in hybrid drug development and ongoing research in hybrid drug discovery. Furthermore, the challenges faced in developing hybrid molecules, such as their design and optimization complexities, bioavailability and pharmacokinetics issues, target identification and validation, and off-target effects, are discussed.

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以嘧啶为基础的药效团为模板开发具有抗癌潜力的混合药物的研究进展。

传统化疗的低疗效和毒性，以及靶向抗癌治疗的耐药性，迫使人们探索和开发抗癌分子。在这个联盟中，混合药物由于其独特的多目标功能和结构多样性，可以作为药物发现的重要线索。考虑到改善的疗效、低毒性和改善的患者依从性，它们似乎提供了额外的优势。在众多被探索的杂环中，嘧啶衍生物由于其有效性和多功能性而成为杂化药物开发的宝贵资源。本文综述了嘧啶这一多种药效团在药物开发中的作用以及杂化药物的概念。本研究涵盖了嘧啶基杂化药物载体的最新进展。它进一步探讨了混合药物开发中的挑战和正在进行的混合药物发现研究。此外，本文还讨论了开发杂交分子所面临的挑战，如它们的设计和优化复杂性、生物利用度和药代动力学问题、靶标识别和验证以及脱靶效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;