Marine Bacterial Compounds Evaluated by In Silico Studies as Antipsychotic Drugs Against Schizophrenia

Abstract

Schizophrenia (SCZ) is one of the brain disorders which affects the thinking and behavioral skills of patients. This disorder comes along with an overproduction of kynurenic acid in the cerebrospinal fluid and the prefrontal cortex of SCZ patients. In this study, marine bacterial compounds were screened for their suitability as antagonists against human kynurenine aminotransferase (hKAT-1) which causes the synthesis of kynurenic acid downstream which ultimately causes the SCZ disorder according to the kynurenic hypothesis of SCZ. The marine actinobacterial compound bonactin shows more promising results than other tested marine compounds such as the histamine H2 blocker famotidine and indole-3-acetic acid (IAC) from docking and in silico toxicological studies carried out here. The obtained results of the Grid-based Ligand Docking with Energetics (Glide) scores of extra-precision (XP) Glide against the target protein hKAT-1 on IAC, famotidine, and bonactin were - 6.581, - 6.500 and - 7.730 kcal/mol where Glide energies were - 29.84, - 28.391, and - 47.565 kcal/mol, respectively. Bonactin is known as an antibacterial and antifungal compound being extracted from a marine Streptomyces sp. Comparing tested compounds against the drug target hKAT-1, bonactin alone showed the best Glide score and Glide energy on the target protein hKAT-1.

Marine-Derived Streptomyces sennicomposti GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking

“…It has a very large genome size, between 6.2 and 12.7 Mb, and 5% of its genome is devoted to the synthesis of secondary metabolites [ 3 , 4 ]. In the past 10 years, the discovery of new compounds from marine bacteria, mainly from the actinobacteria group, has led to the discovery of new antibacterial, antifungal, and antimicrobial compounds [ 5 , 6 , 7 , 8 ], anticancer compounds [ 9 , 10 , 11 ], antioxidants [ 12 , 13 ], anti-complement compounds [ 14 ] and antipsychotic compounds [ 15 ].…”