Synthesis of new chrysin derivatives with substantial antibiofilm activity.

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.

Modulation of S. aureus and P. aeruginosa biofilm: an in vitro study with new coumarin derivatives.

Coumarin is an important heterocyclic molecular framework of bioactive molecules against broad spectrum pathological manifestations. In the present study 18 new coumarin derivatives (CDs) were synthesized and characterized for antibiofilm activity against two model bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. It was observed that all the CDs executed significant effect in moderating activities against both planktonic and biofilm forms of these selected bacteria. Hence, to interpret the underlying probable reason of such antibiofilm effect, in-silico binding study of CDs with biofilm and motility associated proteins of these organisms were performed. All CDs have shown their propensity for occupying the native substrate binding pocket of each protein with moderate to strong binding affinities. One of the CDs such as CAMN1 showed highest binding affinity with these proteins. Interestingly, the findings of in-silico studies coincides the experimental results of antibiofilm and motility affect of CDs against both S. aureus and P. aeruginosa. Moreover, in-silico studies suggested that the antibiofilm activity of test CDs may be due to the interference of biofilm and motility associated proteins of the selected model organisms (PilT from P. aeruginosa and TarK, TarO from S. aureus). The detailed synthesis, characterization, methodology and results of biological screening along with computational studies have been reported. This study could be of greater interest in the context of the development of new anti-bacterial agent in the future.