Discovery of N-[2-(4-methylquinolin-2-yl)phenyl]acetamidine as a new potent nitric oxide synthase inhibitor against glioma progression.

IF 3.8 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2025-08-05 DOI:10.1007/s11030-025-11309-0

Marialucia Gallorini, Rosa Amoroso, Amelia Cataldi, Cristina Maccallini

引用次数: 0

Abstract

Gliomas are aggressive brain tumors with limited treatment options, often leading to poor patient outcomes despite surgery, radiation, and chemotherapy. Current therapies, such as temozolomide and radiation, provide only temporary control, as gliomas frequently develop resistance. Therefore, there is an urgent need for new therapeutics to improve survival and quality of life for patients. In the present study, we explore the hypothesis that the dual inhibition of both the neuronal and inducible nitric oxide synthases could represent a promising therapeutic approach, being these two enzymes often dysregulated in gliomas. To this end, the new quinoline-based compound 3 was synthetized by a simple, innovative and solvent-free procedure. The molecule was a potent dual inhibitor and demonstrated significant antitumor activity against glioma, both as a monotherapy and in combination with temozolomide.

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N-[2-（4-甲基喹啉-2-基）苯基]乙酰脒作为一种新的有效的抗胶质瘤进展的一氧化氮合酶抑制剂的发现。

胶质瘤是侵袭性脑肿瘤，治疗选择有限，尽管手术、放疗和化疗，但往往导致患者预后不佳。目前的治疗方法，如替莫唑胺和放疗，只能提供暂时的控制，因为胶质瘤经常产生耐药性。因此，迫切需要新的治疗方法来提高患者的生存和生活质量。在本研究中，我们探索了神经元型和诱导型一氧化氮合酶的双重抑制可能代表一种有希望的治疗方法的假设，因为这两种酶在胶质瘤中经常失调。为此，采用一种简单、创新、无溶剂的方法合成了新的喹啉基化合物3。该分子是一种有效的双重抑制剂，无论是单独治疗还是与替莫唑胺联合使用，都显示出对胶质瘤的显著抗肿瘤活性。

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;