合成具有抗炎和抗菌作用的新型 2,3,5-三取代噻唑类化合物，对抗临床病原体。

Synthesis of novel 2, 3, 5-tri-substituted thiazoles with anti-inflammatory and antibacterial effect causing clinical pathogens.

机构信息

Department of Pharmaceutical Chemistry, Ali-Allana College of Pharmacy, Akkalkuwa, 425415, Nandurbar, Maharashtra, India.

出版信息

J Infect Public Health. 2020 Apr;13(4):472-479. doi: 10.1016/j.jiph.2020.02.002. Epub 2020 Mar 2.

DOI:10.1016/j.jiph.2020.02.002

PMID:32139293

Abstract

BACKGROUND

The present work is an extension of ongoing efforts toward the development and identification of new molecules as monotherapy displaying anti-inflammatory and anti-infective activities and a wide-range of gastrointestinal selectivity. A series of novel set of trisubstituted thiazole compounds (AR-17a to AR-27a) have synthesized and evaluated for their in-vitro and in-vivo anti-inflammatory activities. Synthesized trisubstituted thiazole compounds were also evaluated for their potential antibacterial activity against clinical pathogens causing infectious disease.

MATERIAL AND METHOD

The structures of synthesized compounds were characterized by FTIR, H NMR, Mass spectroscopic techniques and evaluated for their in-vitro and in-vivo anti-inflammatory effects using the human red blood cell (HRBC) membrane stabilization method and a carrageenan-induced rat paw oedema model, respectively, Diclofenac sodium and Ibuprofen were used as standard drugs. The synthesized compounds AR-17atoAR-27a screened for their in-vitro antibacterial activity against the gram-positive bacteria Staphylococcus aureus (ATCC25923) and Enterococcus faecalis (ATCC29212) and the gram-negative bacteria Escherichia coli (ATCC8739) and Pseudomonas aeruginosa (ATCC9027) using ciprofloxacin and cefdinir as standard drugs.

RESULT

Compounds AR-17a and AR-27a elicited maximum anti-inflammatory activity, providing 59% and 61% protection at 20mg/kg, respectively, in the inflamed paw model. Among the tested compounds, AR-17a (6.25), (54) and AR-27a (1.56), (52) had the least minimum inhibitory concentration values and the highest zone of inhibition, indicating their marked antibacterial activities. The lowest conc. were observed at 1.56, 6.25μg/mL for inhibition of bacteria by most of the compounds.

CONCLUSION

Novel set of trisubstituted thiazole compounds (AR-17a to AR-27a) have synthesized and characterized successfully. The preliminary screening revealed that these compounds possess promising anti-inflammatory and antibacterial activities. In addition, the objective of the study was achieved with few of the promising structures like AR-17a to AR-27a, which are prove to be potential monotherapy candidates for the treatment of chronic inflammatory diseases and bacterial infections.

摘要

背景

本工作是正在进行的努力的延伸，旨在开发和鉴定新的单药分子，这些分子具有抗炎和抗感染活性以及广泛的胃肠道选择性。一系列新型三取代噻唑化合物（AR-17a 至 AR-27a）已被合成并评估其体外和体内抗炎活性。合成的三取代噻唑化合物也评估了其对引起传染病的临床病原体的潜在抗菌活性。

材料和方法

合成化合物的结构通过傅里叶变换红外光谱（FTIR）、核磁共振（H NMR）、质谱分析技术进行了表征，并通过人红细胞（HRBC）膜稳定化方法和角叉菜胶诱导的大鼠足肿胀模型分别评估其体外和体内抗炎作用，双氯芬酸钠和布洛芬用作标准药物。合成的化合物 AR-17a 至 AR-27a 筛选对革兰氏阳性菌金黄色葡萄球菌（ATCC25923）和粪肠球菌（ATCC29212）以及革兰氏阴性菌大肠杆菌（ATCC8739）和铜绿假单胞菌（ATCC9027）的体外抗菌活性，使用环丙沙星和头孢地尼作为标准药物。

结果

化合物 AR-17a 和 AR-27a 在 20mg/kg 时在炎症性足模型中分别产生最大抗炎活性，提供 59%和 61%的保护。在所测试的化合物中，AR-17a（6.25），（54）和 AR-27a（1.56），（52）具有最低的最小抑菌浓度值和最高的抑菌圈，表明它们具有显著的抗菌活性。大多数化合物抑制细菌的最低浓度为 1.56、6.25μg/mL。