Vishu Mehra

Discovery of highly selective 7-chloroquinoline-thiohydantoins with potent antimalarial activity

A series of C-3 thiourea functionalized β-lactams, β-lactam-7-chloroquinoline conjugates and 7-chloroquinoline-thiohydantoin derivatives were prepared with the aim of probing antimalarial structure-activity relationships. 7-Chlorquinoline-thiohydantoin derivatives were found to be potent inhibitors of cultured Plasmodium falciparum, with the most potent and non-cytotoxic compound exhibiting an IC50 of 39.8 nM. Studies of β-hematin formation suggested that inhibition of haemozoin formation could be primary mechanism of action, with IC50 values comparable to those of chloroquine. Evaluation of cytotoxicity against HeLa cells demonstrated high selective indices.

Design and synthesis of β-amino alcohol based β-lactam–isatin chimeras and preliminary analysis of in vitro activity against the protozoal pathogen Trichomonas vaginalis

We have described the synthesis of β-amino alcohol based β-lactam–isatin chimeras along with their in vitro evaluation against T. vaginalis. SAR studies showed dependence of activity on concentration as well as substituent on N-1 of β-lactam and C-5 of isatin with preference for a chloro-substituent for good activity.

Triflic acid promoted fries rearrangement of C-3 vinyl/isopropenyl-azetidin-2-ones: single-pot synthesis of C-3 functionalized-2-aryl-2,3-dihydro-quinoline-4(1H)-ones

The β-lactam-synthon-interceded synthesis of C-3 functionalized 2-aryl-2,3-dihydro-quinoline-4(1H)-ones has been described via the Fries rearrangement of C-3 vinyl/isopropenyl substituted β-lactams. The reaction at 0 °C resulted in the isolation of a tautomeric mixture, and the preferential formation of the conjugated product was observed at higher temperatures. Density functional theory (DFT) calculations and molecular dynamics (MD) simulations were additionally performed to explain the preferential formation of product 2 over 3. The proposed mechanism was further validated via the base-induced isomerisation of the mixture of 2a and 3a.