Anti-proliferative potential of cyclotetrapeptides from Bacillus velezensis RA5401 and their molecular docking on G-Protein-Coupled Receptors

Abstract Elucidation of bioactive chemical compounds from rhizobacteria is highly utilized in pharmaceuticals and naturopathy, due to their health benefits to human and plants. In current study, four cyclopeptides along with one phenyl amide were isolated from the ethyl acetate extract of Bacillus velezensis sp. RA5401. Their structures were determined and characterized as cycle (L-prolyl-L-leucyl) 2 ( 1 ), cyclo (L-prolyl- l -valine) 2 ( 2 ), cycle (L-phenylanalyl-L-propyl) 2 ( 3 ), cyclo (D-pro-L-tyr-L-pro-L-tyr) 2 ( 4 ) and N-(2-phenylethyl)acetamide ( 5 ) on the basis of electron spray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR) techniques and comparison with the literature data. The five compounds have been isolated for the first time from this species. The effect of various concentrations of these compounds on the proliferation of MDA-MB-231 breast cancer cells was examined. It was found that 1 and 2 induced concentration-independent anti-proliferative effects, while 3 , 4 and 5 inhibited cancer cell proliferation in a concentration-dependent manner. Furthermore, to determine the suitable binding targets of these compounds within cancer cell line, detailed target prediction and comparative molecular-docking studies were performed. The compounds 1 and 2 hit intracellular anti-cancer targets of proteases family, while compounds 3 , 4 and 5 interacted with different membrane receptors of G-Protein-Coupled Receptors (GPCRs). In conclusion, the Bacillus velezensis RA5401 can be an ideal strain to produce anti-proliferative constituents at industrial scale.