Possible inhibitory effects of hoslundal, hoslundin and hoslunddiol on human lactate dehydrogenases: a bioinformatics proof

Abstract

The development of anti-malarial drugs is of great importance due to the detrimental effects of this disease all around the world. In recent years, bioinformatics tools provide considerable contributions to develop new small molecules which have important bioactivities against many bio-targets. However, biases in the methodologies or aims of the studies in which in silico tools are used may reveal problematic cases. Hoslundal, hoslundin, and hoslunddiol were proposed by Shadrack et al. (2016) to inhibit Plasmodium falciparum lactate dehydrogenase (Pf-LDH) to fight malaria. But these molecules may have potential to inhibit mammalian LDHs. To investigate whether these molecules have inhibitions on mammalian LDHs or not, we studied a comprehensive and comparative molecular docking studies as described in the present paper. According to the results, the vina scores of hoslundal without NADH for Pf-LDH, HM-LDH, HH-LDH were found as -7.5, -7.6 and -8.2 kJ/mol, respectively. Moreover, multiple sequence alignment analysis reveals high similarities among sequences. In the light of molecular studies, hoslundal were found to be connected to Pf-LDH, HM-LDH, HH-LDH (31, 26, 34), (2, -7, 154), (11, 41, 54), respectively. In conclusion, novel small molecules which are developed via in silico tools could show excellent activities against bio-targets of the pathogenic microorganisms. However, it should not be forgotten that active site of the enzymes is conserved, therefore, after a possible proposal of small molecule, its molecular docking and also Swiss-ADME studies should be necessarily carried out.