Synthesis, anti-leishmanial and molecular docking study of bis-indole derivatives

Abstract

We have synthesized new series of bisindole analogs ( 1 – 27 ), characterized by 1 HNMR and HR-EI-MS and evaluated for their anti-leishmanial potential. All compounds showed outstanding inhibitory potential with IC 50 values ranging from 0.7 ± 0.01 to 13.30 ± 0.50 µM respectively when compared with standard pentamidine with IC 50 value of 7.20 ± 0.20 µM. All analogs showed greater potential than standard except 10 , 19 and 23 when compared with standard. Structure activity relationship has been also established for all compounds. Molecular docking studies were carried out to understand the binding interaction of active molecules. Electronic supplementary material The online version of this article (10.1186/s13065-019-0617-4) contains supplementary material, which is available to authorized users.

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

“…Inspired by the biological potential of natural bis-indole compounds, Taha et al synthetized 27 synthetic bis-indole analogs and investigated their antileishmanial activity [ 125 ]. The compounds were obtained via a simple three-step procedure, starting with the condensation of two equivalents of indole with methyl-4-formylbenzoate ( 200 ) ( Scheme 22 ) [ 125 ].…”

“…Inspired by the biological potential of natural bis-indole compounds, Taha et al synthetized 27 synthetic bis-indole analogs and investigated their antileishmanial activity [ 125 ]. The compounds were obtained via a simple three-step procedure, starting with the condensation of two equivalents of indole with methyl-4-formylbenzoate ( 200 ) ( Scheme 22 ) [ 125 ]. In sequence, the intermediate was treated with hydrazine hydrate to generate the acyl hydrazide that was converted to the final products 203 by the reaction with different isothiocyanates [ 125 ].…”

“…The compounds were obtained via a simple three-step procedure, starting with the condensation of two equivalents of indole with methyl-4-formylbenzoate ( 200 ) ( Scheme 22 ) [ 125 ]. In sequence, the intermediate was treated with hydrazine hydrate to generate the acyl hydrazide that was converted to the final products 203 by the reaction with different isothiocyanates [ 125 ]. In comparison to the standard drug (pentamidine), most derivatives potently inhibited the in vitro growth of the parasite.…”

“…The SAR study was able to identify structural features that most impacted the activity. In particular, the presence of vicinal dihydroxy systems is the most relevant feature [ 125 ]. Docking studies with the most active compound indicated that compounds of this class tend to interact with key residues on pteridine reductase, which could explain the inhibitory activity [ 125 ].…”

Phenotype Screening of an Azole-bisindole Chemical Library Identifies URB1483 as a New Antileishmanial Agent Devoid of Toxicity on Human Cells

“…Very recently, the group of Taha has reported several phenyl-aminothiazole-DIM derivatives as potent antileishmanial agents. 15 In particular, compound 6 ( Figure 2 ) has shown an outstanding effect on the protozoa with a submicromolar IC 50 value. The authors claimed that this new class of compounds may inhibit the pteridine reductase.…”