Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons.

ABSTRACT:

Background

The development of 3, 3'-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 µM concentration.

Methodology/principal findings

In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,2'-diphenyl 3,3'-diindolyl methane), DMDIM (2,2'-dimethyl 3,3'-diindolyl methane) and DMODIM (5,5'-dimethoxy 3,3'-diindolyl methane) from parent compo

SUBMITTER: Roy A 

PROVIDER: S-EPMC3236199 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature