Isatin, chemically an indole-1H-2,3-dione, is recognised as one of the most attractive therapeutic fragments in drug design and development. The template has turned out to be exceptionally useful for developing new anticancer scaffolds, as evidenced by the increasing number of isatin-based molecules which are either in clinical use or in trials. Apart from its promising antiproliferative properties, isatin has shown potential in treating Neglected Tropical Diseases (NTDs) not only as a parent core, but also by attenuating the activities of various pharmacophores. The objective of this mini-review is to keep readers up to date on the latest developments in the biological potential of isatin-based scaffolds, targeting cancer and NTDs such as tuberculosis, malaria, and microbial infections.
In the search of new antiplasmodial
agents, a multitargeted approach
was used in the synthesis of triazolopyrimidine- and 4-aminoquinolines-based
hybrids. In vitro antiplasmodial evaluation on chloroquine-sensitive
(3D7) and -resistant (W2) P. falciparum strains identified
triazolopyrimidine-4-aminoquinoline hybrids to be the most potent
in the series, outperforming bis-triazolopyrimidines. The active compounds
were subjected to mechanistic studies with the plausible and expected
targets including heme, PfCRT, and PfDHODH, that eventually validated
the biological data. The active compound surpassed the antimalarial
drug CQ by inhibiting the parasite’s cellular process (hemozoin
formation) and parasitic enzymes (PfCRT and PfDHODH), as confirmed
by UV–vis and molecular modeling studies.
A library of quinoline‐based hydrazones bearing 1H‐1,2,3‐triazole core was designed, synthesized, and evaluated for their antiplasmodial activity against the drug‐resistant Plasmodium falciparum W2 strain. The inclusion of pyrazine‐2‐carboxylic acid with a flexible propyl spacer afforded the most active scaffold with an IC50 value of 0.26 μM. Mechanistically, the compound inhibited heme to hemozoin formation, as demonstrated by UV–vis and mass spectral studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.