Synthesis of novel indolo[3,2-c]isoquinoline derivatives bearing pyrimidine, piperazine rings and their biological evaluation and docking studies against COVID-19 virus main protease

Abstract

A series of hybrid indolo[3,2-c]isoquinoline (δ-carboline) analogs incorporating two pyrimidine and piperizine ring frameworks were synthesized. Intending biological activities and SAR we propose replacements of fluorine, methyl and methoxy of synthetic compounds for noteworthy antimicrobial, antioxidant, anticancer and anti-tuberculosis activities. Among these compounds 3a, 4a and 5e were progressively strong against E. coli and K. pneumonia. Whereas, compounds 4a, 5a and 6a with addition of various functional groups (OCH3, CH3) were excellent against S. aureus and B. subtilis. Compound 5c exhibited strong RSA and dynamic ferrous ion (Fe2+) metal chelating impact with IC50 of 7.88 ± 0.93 and 4.06 ± 0.31 µg/mL, respectively. Compound 5e was considerably cytotoxic against all cancer cells displaying activity better than the standard drug. Compounds 6b and 6e inhibited M. tuberculosis (MIC 1.0 mg/L) considerably. Molecular docking studies indicate that compounds 4d, 5a, 5b, 6b and 6f exhibited good interactions with 6LZE (COVID-19) and 6XFN (SARS-CoV-2) at active sites. The structure of the synthesized compounds were elementally analyzed using IR, 1H, 13C NMR and mass spectral information.