Discovery of antimalarial drugs from secondary metabolitesin actinomycetes culture library

Abstract

Abstract Background Scientists renewed interest in the discovery of drugs from natural products and therefore they continue to play a key role as a potential source of biologically active substances for the discovery of new drugs. This study aimed to identify the secondary metabolite of actinomycete library extracts that are potent against asexual stages of Plasmodium falciparum (P. falciparum). Methods Isolation of secondary metabolite of actinomycete library extracts were conducted using ethyl acetate extraction from the culture supernatant. A comprehensive screening was performed to identify novel antimalarial compounds from secondary metabolites in Actinomycete library extracts (n = 28). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) lines of P. falciparum. The cytotoxicity was also evaluated using primary adult mouse brain (AMB) cells. Results Out of 28 secondary metabolites of actinomycete extracts, seventeen of which showed a parasite growth inhibition > 50% at 50 µg/mL, nine hits were identified with the IC50 < 10 µg/mL, seven of which were suppressing the parasite significantly with the IC50 < 5 µg/mL. The extracts from Streptomyces aureus strains HUT6003 (Extract ID number: 2) and antibioticus HUT6035 (8), and Streptomyces sp. strains GK3 (26) and GK7 (27), were found to have the most potent antimalarial activity with the IC50 0.39, 0.09, 0.97, and 0.36 µg/mL (against 3D7), and 0.26, 0.22, 0.72, and 0.21 µg/mL (against Dd2), respectively. Among them, Streptomyces antibioticus strain HUT6035 (8) showed the highest antimalarial activity with IC50 0.09 against 3D7 and 0.22 against Dd2 with a selective index (SI) of 188 and 73.7, respectively. Conclusion Secondary metabolite(s) of actinomycete extracts showed promising antimalarial activity against 3D7 and Dd2 lines of P. falciparum in vitro with minimal toxicity. Therefore, a secondary metabolite of actinomycete extracts represents an excellent starting point toward the development of antimalarial drug leads.