The Synthesis and Biological Evaluation of 2-(1<i>H</i>-Indol-3-yl)quinazolin-4(3<i>H</i>)-One Derivatives

The treatment of many bacterial diseases remains a significant problem due to the increasing antibiotic resistance of their infectious agents. Among others, this is related to Staphylococcus aureus , especially methicillin-resistant S. aureus (MRSA) and Mycobacterium tuberculosis . In the present article, we report on antibacterial compounds with activity against both S. aureus and MRSA. A straightforward approach to 2-(1 H -indol-3-yl)quinazolin-4(3 H )-one and their analogues was developed. Their structural and functional relationships were also considered. The antimicrobial activity of the synthesized compounds against Mycobacterium tuberculosis H 37 Rv, S. aureus ATCC 25923, MRSA ATCC 43300, Candida albicans ATCC 10231, and their role in the inhibition of the biofilm formation of S. aureus were reported. 2-(5-Iodo-1 H -indol-3-yl)quinazolin-4(3 H )-one ( 3k ) showed a low minimum inhibitory concentration (MIC) of 0.98 μg/mL against MRSA. The synthesized compounds were assessed via molecular docking for their ability to bind long RSH (RelA/SpoT homolog) proteins using mycobacterial and streptococcal (p)ppGpp synthetase structures as models. The cytotoxic activity of some synthesized compounds was studied. Compounds 3c , f , g , k , r , and 3 z displayed significant antiproliferative activities against all the cancer cell lines tested. Indolylquinazolinones 3b , 3e , and 3g showed a preferential suppression of the growth of rapidly dividing A549 cells compared to slower growing fibroblasts of non-tumor etiology.