RESUMEN
Lewis-acid cascade reactions promoted by BF3·OEt2 are reported for the synthesis of highly substituted pyrrolo[1,2-a]indoles and congeners of benzofuro[2,3-b]indoles. These reactions are highly regio- and diastereoselective towards generating up to five contiguous stereogenic centers, including two vicinal quaternary centers. Furthermore, an established cascade approach and the mechanism proposed herein are well supported by quantum chemistry calculations. In addition, a self-dimerization intermediate was trapped and isolated to establish a strategy for potential access to both pyrrolo and benzo indole derivatives, leaving sufficient freedom for broadening. Furthermore, in-silico molecular docking and all atomistic molecular dynamic (MD) simulation analysis suggests that the synthesized pyrrolo[1,2-a]indole derivatives stably bind at the active site of the mycobacterial secreted tyrosine phosphatase B (MptpB) enzyme, an emerging anti-mycobacterial drug target. Deep learning-based affinity predictions and MMPBGBSA-based energy calculations of the docked poses are presented herein.
RESUMEN
Fruits and vegetables contain a variety of ingredients that exhibit chemopreventive effects against an array of xenobiotics. In the present study, the antigenotoxic potential of lupeol, a triterpene, and mango pulp extract (MPE) was evaluated in Swiss albino mice. Benzo[a]pyrene (B[a]P), a well-known mutagen, was given at a single dose of 100 mg/kg body weight intraperitoneally. Pretreatment with lupeol (1 mg/animal) and MPE (1 mL, 20%) was given through oral intubation for 7 days prior to B[a]P administration. Animals from all the groups were killed at sampling time of 24 h and their bone marrow tissue was analyzed for chromosomal damage and micronuclei induction. In B[a]P-treated animals a significant induction of chromosomal aberration and micronuclei was recorded, with a decrease in mitotic index. In lupeol- or MPE-supplemented groups, a significant decrease in B[a]P-induced clastogenicity was recorded. The incidence of aberrant cells and micronuclei was found to be reduced by both lupeol and MPE when compared to the B[a]P-treated group. The anti-cytotoxic effects of lupeol or MPE were also evident, as observed by significant increase in mitotic index. Thus, results of the present investigation revealed that lupeol and MPE have protective effects against B[a]P-induced clastogenic changes in Swiss albino mice.