Synthesis and Cyclooxygenase-2 Inhibitory Activity Evaluation of Some Pyridazine Derivatives

IF 0.3 Q4 CHEMISTRY, MULTIDISCIPLINARY

Oriental Journal Of Chemistry Pub Date : 2023-10-30 DOI:10.13005/ojc/390504

Mohd Imran, Abida Ash Mohd, Naira Nayeem, Nawaf M. Al-Otaibi, Malik Homoud, Muhannad Thafi Alshammari

{"title":"Synthesis and Cyclooxygenase-2 Inhibitory Activity Evaluation of Some Pyridazine Derivatives","authors":"Mohd Imran, Abida Ash Mohd, Naira Nayeem, Nawaf M. Al-Otaibi, Malik Homoud, Muhannad Thafi Alshammari","doi":"10.13005/ojc/390504","DOIUrl":null,"url":null,"abstract":"This work aimed to discover safe and effective pyridazine-based cyclooxygenase-2 (COX-2) inhibitors. Thirty-three pyridazine-based compounds (compounds 1 to 33) were designed. The in silico studies were conducted to predict their toxicity, docking scores (DS), pharmacokinetic parameters, and drug-likeliness properties compared to celecoxib. Based on the safety and efficacy data obtained by in silico studies, four compounds (7, 12, 16, and 24) were synthesized, and the spectral analysis confirmed their chemical structures. Additionally, the in vitro COX-2 inhibitory activity of these four compounds was evaluated. Eleven compounds were predicted as non-toxic compounds. The DS of four compounds, 7 (DS = -9.72 kcal/mol), 12 (DS = -10.48 kcal/mol), 16 (DS = -9.71 kcal/mol), and 24 (DS = -9.46 kcal/mol), was better than celecoxib (DS = -9.15). These compounds (7, 12, 16, and 24) also demonstrated better oral absorption (83.53% each) than celecoxib (79.20%) in addition to their promising drug-likeliness properties. The compounds 7 (101.23%; p < 0.05), 12 (109.56%; p < 0.05), 16 (108.25%; p < 0.05), and 24 (103.90%; p < 0.05) also exhibited superior COX-2 inhibition to celecoxib (100%; p < 0.05). Compounds 7, 12, 16, and 24 are useful lead compounds in developing drugs for various diseases in which high levels of COX-2 are implicated.","PeriodicalId":19599,"journal":{"name":"Oriental Journal Of Chemistry","volume":"1 1","pages":"0"},"PeriodicalIF":0.3000,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oriental Journal Of Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.13005/ojc/390504","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

This work aimed to discover safe and effective pyridazine-based cyclooxygenase-2 (COX-2) inhibitors. Thirty-three pyridazine-based compounds (compounds 1 to 33) were designed. The in silico studies were conducted to predict their toxicity, docking scores (DS), pharmacokinetic parameters, and drug-likeliness properties compared to celecoxib. Based on the safety and efficacy data obtained by in silico studies, four compounds (7, 12, 16, and 24) were synthesized, and the spectral analysis confirmed their chemical structures. Additionally, the in vitro COX-2 inhibitory activity of these four compounds was evaluated. Eleven compounds were predicted as non-toxic compounds. The DS of four compounds, 7 (DS = -9.72 kcal/mol), 12 (DS = -10.48 kcal/mol), 16 (DS = -9.71 kcal/mol), and 24 (DS = -9.46 kcal/mol), was better than celecoxib (DS = -9.15). These compounds (7, 12, 16, and 24) also demonstrated better oral absorption (83.53% each) than celecoxib (79.20%) in addition to their promising drug-likeliness properties. The compounds 7 (101.23%; p < 0.05), 12 (109.56%; p < 0.05), 16 (108.25%; p < 0.05), and 24 (103.90%; p < 0.05) also exhibited superior COX-2 inhibition to celecoxib (100%; p < 0.05). Compounds 7, 12, 16, and 24 are useful lead compounds in developing drugs for various diseases in which high levels of COX-2 are implicated.

查看原文本刊更多论文

吡嗪类衍生物的合成及环氧合酶-2抑制活性评价

本工作旨在发现安全有效的吡啶类环氧化酶-2 (COX-2)抑制剂。设计了33个吡嗪类化合物(化合物1 ~ 33)。与塞来昔布相比，进行了计算机研究来预测它们的毒性、对接评分(DS)、药代动力学参数和药物可能性特性。基于硅实验获得的安全性和有效性数据，合成了4个化合物(7、12、16和24)，并通过光谱分析确定了它们的化学结构。此外，我们还对这四种化合物的体外COX-2抑制活性进行了评价。11种化合物被预测为无毒化合物。化合物7 (DS = -9.72 kcal/mol)、12 (DS = -10.48 kcal/mol)、16 (DS = -9.71 kcal/mol)和24 (DS = -9.46 kcal/mol)的DS均优于塞来昔布(DS = -9.15)。这些化合物(7、12、16和24)也表现出比塞来昔布(79.20%)更好的口服吸收(各为83.53%)。化合物7 (101.23%;p & lt;0.05)， 12 (109.56%;p & lt;0.05)， 16 (108.25%;p & lt;0.05)， 24 (103.90%;p & lt;0.05)也表现出优于塞来昔布的COX-2抑制作用(100%;p & lt;0.05)。化合物7、12、16和24是有用的先导化合物，可用于开发与高水平COX-2有关的各种疾病的药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oriental Journal Of Chemistry CHEMISTRY, MULTIDISCIPLINARY-

自引率

20.00%

发文量

172

期刊介绍： Oriental Journal of Chemistry was started in 1985 with the aim to promote chemistry research. The journal consists of articles which are rigorously peer-reviewed. The journal was indexed in Emerging Science citation index in 2016. The Editorial board member consists of eminent international scientist in all fields of Chemistry. Details of each member and their contact information is mentioned in website. The journal has thorough ethics policies and uses plagiarism detection software(ithenticate) to screen each submission. The journal has recently partnered with publons as a part of making our reviews more transparent. The journal has recently incorporated PlumX for article level matrix. The journal is promoting research on all social and academic platforms mentioned in PlumX guidelines. The journal uses google maps to improve on the geographical distribution of Editorial board members as well as authors.