Design, synthesis, and biological evaluation of 3,3′-diindolylmethane <i>N</i>-linked glycoconjugate as a leishmanial topoisomerase IB inhibitor with reduced cytotoxicity
Parampreet Kour, Pallavi Saha, S.K. Bhattacharya, Diksha Kumari, Abhipsa Debnath, Amit Kumar Roy, Deepak K. Sharma, Debaraj Mukherjee, Kuljit Singh
Abstract
glycoside of potent compound 3d using indole-indoline conversion, Fischer-type glycosylation, 2,3-dichloro-5,6-dicyano-1,4-benzoquionone (DDQ) oxidation, and molecular iodine catalyzed coupling with a suitable aldehyde in reasonable overall yield. The biological evaluation revealed that glycosides had reduced cytotoxic effects on the J774A.1 macrophage cell line. The enzyme inhibition study confirms that the glycoside derivatives have significant inhibitory activity against the leishmanial topoisomerase IB enzyme. Molecular docking further displayed the better binding efficiency of glycoside 13 with the target enzyme, suggesting the involvement of more H-bond interactions in the case of glycosides as compared to free drugs. Therefore, this work helps in proposing the fact that the addition of sugar moieties adds some favorable characteristics to free inhibitors, making it a promising approach for future clinical diagnostic and therapeutic applications, which can prove to be a valuable arsenal in combating such neglected diseases.