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Computer-based simulation of the interaction of amidrazone hydrogen halides with target proteins


A.S. Senina(1), K.M. Pats(2), A.V. Moskvin(1), Yu.B. Porozov(2, 3) 1-Saint Petersburg State Chemopharmaceutical University, 14, Prof. Popov St., Saint Petersburg 197376, Russian Federation; 2-Saint Petersburg National Research University of Information Technologies, Mechanics. and Optics (ITMO University) 49, Kronverksky Prospect, Saint Petersburg 197101, Russian Federation; 3-I.M. Sechenov First Moscow State Medical University (Sechenov University), 8, Trubetskaya St., Build. 2, Moscow 119991, Russian Federation

Introduction. A number of biologically active amidrazone hydrogen halides have been synthesized, which are a promising group to design agents having antibacterial and antifungal activities. Objective: to make a prognosis and computer-based simulation of the interaction of synthesized compounds with bacterial and fungal targets. Material and methods. Computer-based simulation of the interaction of amidrazone derivatives with potential bacterial and fungal targets was performed for the obtained compounds, by using the PASS, PASS Targets, and Schrödinger Small-Molecule Drug Discovery Suite Release 2018-2 software. Results. The investigators obtained a computer-based prediction of the spectrum of potential biological activity of the synthesized amidrazone hydrogen halides 3a-f. The PASS Targets program was used to propose target proteins from microorganisms (cystathionine-β-lyase (1CL2) from Escherichia coli, phosphopantetheinyl transferase (1QR0) from Bacillus cereus, exo-β-(1,3)-glucanase (2PB1) from Candida albicans, and dehydrosqualene synthase (3ACX) from Staphylococcus aureus) to simulate the interaction with amidrazons 3a-f. Two targets (2PB1 and 3ACX) were ascertained to be promising for the design of novel antibiotic drugs based on amidrazone. The investigation results can be used as a targeted search for and synthesis of low-toxic effective antimicrobial agents. Conclusion. The predictive computer-based simulation of a number of novel compounds (amidrazone hydrogen halides – 3) based on N'-arylbenzenecarboximidohydrazides could determine possible targets for their interaction with amidrazone derivatives. There is evidence that they are important in the vital processes of the microorganisms in question. The targets that can be a goal for compounds of the amidrazone class are selected.

amidrazone hydrogen halides
biological activity
computer-based simulation

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