Department of Chemistry, Tripura University, Suryamaninagar, Tripura, 799022, India.
Department of Biotechnology, School of Life Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, 226025, India.
Mol Divers. 2022 Feb;26(1):137-156. doi: 10.1007/s11030-020-10162-7. Epub 2021 Jan 12.
Multidrug resistance mechanism of microorganisms towards conventional antimicrobials nowadays faces a common health problem. So, searching and development of new antibacterials are in the frontier areas of biochemistry. Functionalizations of various natural products or synthesis of compounds through molecular modeling followed by virtual screening are the ways to obtain potential leads. Chrysin is one of the plant secondary metabolites and is ubiquitously present in majority of plants. It has multi-dimensional potentiality however, with a very low bioavailability causing a very low efficacy. Very few chrysin derivatives possessing antimicrobial activity with a low anti-biofilm efficacy have been found in the literature. Thus, it has been attempted to synthesize a series of new chrysin derivatives (CDs). In this study, twenty-two new derivatives have been synthesized via its 7-OH modulation and antibiofilm activity was evaluated against a model bacterium viz. Escherichia coli MTCC 40 (Gram negative). Eleven CDs coded as 2a, 2b, 2c, 2e, 2f, 2g, 2h, 2i, 3j, 3k and 3l have been found more potent compared to chrysin (precursor of CDs) against planktonic form of E. coli. Biofilm inhibition studies indicated a noteworthy results for 2a (93.57%), 2b (92.14%), 2f (92.14%) and 3l (93.57%) compared to chrysin (33.57%). E. coli motility was also highly restricted by 2a, 2b, 2f and 3l than chrysin at their sub-inhibitory concentrations. Solubility studies indicated an extended-release of 2a, 2b, 2f and 3l in physiological systems. Relatively higher bioavailability of 2a, 2b, 2f and 3l than chrysin was revealed from the dissolution experiments and was further validated through in silico ADME-based SAR analysis. Hence, this study is more interesting in regard to antibacterial potentiality of chrysin derivatives against Escherichia coli MTCC 40 (Gram negative). Thus, this article might be useful for further design and development of new leads in the context of biofilm-associated bacterial infections.
如今，微生物对传统抗菌药物的多药耐药机制是一个共同的健康问题。因此，新抗菌药物的搜索和开发是生物化学的前沿领域。通过分子模拟对各种天然产物进行功能化或合成化合物，然后进行虚拟筛选，是获得潜在先导物的方法。白杨素是植物次生代谢物之一，广泛存在于大多数植物中。它具有多维的潜力，但是生物利用度非常低，导致疗效非常低。文献中发现的具有抗菌活性且抗生物膜效果低的白杨素衍生物很少。因此，人们试图合成一系列新的白杨素衍生物 (CDs)。在这项研究中，通过 7-OH 调节合成了二十二种新的衍生物，并评估了它们对模式细菌大肠杆菌 MTCC 40（革兰氏阴性）的抗生物膜活性。与白杨素（CDs 的前体）相比，编码为 2a、2b、2c、2e、2f、2g、2h、2i、3j、3k 和 3l 的 11 种 CDs 对大肠杆菌浮游生物形式的活性更强。生物膜抑制研究表明，与白杨素（33.57%）相比，2a（93.57%）、2b（92.14%）、2f（92.14%）和 3l（93.57%）的抑制效果更为显著。与白杨素相比，在亚抑菌浓度下，2a、2b、2f 和 3l 也高度限制了大肠杆菌的运动性。溶解度研究表明，2a、2b、2f 和 3l 在生理系统中具有延长释放的特性。从溶解实验中发现 2a、2b、2f 和 3l 的相对较高的生物利用度高于白杨素，并通过基于体内 ADME 的 SAR 分析进行了进一步验证。因此，与大肠杆菌 MTCC 40（革兰氏阴性）相比，这项研究在白杨素衍生物的抗菌潜力方面更有趣。因此，本文对于针对生物膜相关细菌感染的新型先导物的进一步设计和开发可能有用。
