ELECTRON WITHDRAWING GROUP EFFECT ON BIOLOGICAL ACTIVITIES OF PYRIMIDINE HYBRIDS AS POTENTIAL ANTI-MATRIX METALLOPROTEINASE-7

IF 0.5 4区化学 Q4 CHEMISTRY, MULTIDISCIPLINARY

Quimica Nova Pub Date : 2023-10-09 DOI:10.21577/0100-4042.20230055

A. Oyebamiji, S. Akintelu, K. Odelade, B. Adetuyi, E. Akintayo, C. Akintayo, B. Semire, J. Babalola

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Abstract

We investigated the effect of both electron donating group and e//lectron withdrawing group on biological activity of pyrimidine-based compounds as metalloproteinase-7 inhibitors and predicting a library of drug-like compounds with potent cytotoxicity using in silico approach. The selected compounds were optimized and subjected to both docking as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) analyzes. We observed that the addition of electron withdrawing group (–CF3) to the predicted pyrimidine-based compound induced a radical improvement in the hydrogen bond strength with Leu181 and Ala182 in matrix metalloproteinase-7. Also, communal orientation of 2-mercapto-4-(3-(trifluoromethyl)phenyl)-6-((4-(trifluoromethyl)phenyl)amino) pyrimidine-5-carbonitrile (PC10) and matrix metalloproteinase-7 showed improved binding tendency with calculated binding affinity value of −10.2 kcal mol-1 than other studied compounds. Our findings may open door for the design and development of library of efficient pyrimidine-based drug-like compounds as potential anti-cancer agents.

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吸电子基团对嘧啶杂合体潜在抗基质金属蛋白酶活性的影响

我们研究了供电子基团和e//吸电子基团对嘧啶类金属蛋白酶-7抑制剂生物活性的影响，并用计算机方法预测了具有强细胞毒性的类药物化合物文库。对所选化合物进行了优化，并进行对接、吸收、分布、代谢、排泄和毒性(ADMET)分析。我们观察到，在预测的嘧啶基化合物上加入吸电子基团(-CF3)可以显著提高基质金属蛋白酶-7中与Leu181和Ala182的氢键强度。此外，2-巯基-4-(3-(三氟甲基)苯基)-6-((4-(三氟甲基)苯基)氨基-5-碳腈(PC10)与基质金属蛋白酶-7的共取向结合倾向更好，计算出的结合亲和力值为- 10.2 kcal mol-1。我们的研究结果可能为设计和开发高效的嘧啶类药物类化合物库作为潜在的抗癌药物打开了大门。

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

Quimica Nova 化学-化学综合

CiteScore

1.60

自引率

12.50%

发文量

审稿时长

2-4 weeks

期刊介绍： Química Nova publishes in portuguese, spanish and english, original research articles, revisions, technical notes and articles about education in chemistry. All the manuscripts submitted to QN are evaluated by, at least, two reviewers (from Brazil and abroad) of recognized expertise in the field of chemistry involved in the manuscript. The Editorial Council can be eventually asked to review manuscripts. Editors are responsible for the final edition of QN.