STRUCTURAL PROPERTIES AND BIOLOGICAL ACTIVITY PREDICTIONS OF SOME BARBITURATE COMPOUNDS


İzmirli M., Aygün M., Fırıncı E.

TURKISH PHYSICAL SOCIETY 37 th INTERNATIONAL PHYSICS CONGRESS, Muğla, Turkey, 1 - 05 September 2021, pp.83

  • Publication Type: Conference Paper / Summary Text
  • City: Muğla
  • Country: Turkey
  • Page Numbers: pp.83
  • Dokuz Eylül University Affiliated: Yes

Abstract

Researchers are paying attention to barbituric acid and its synthetic derivatives because of their unique structural features and pharmaceutical uses. By substituting in the C5 and N1/N3 positions of the barbituric acid ring, various derivatives of barbituric acid were obtained, yielding compounds with a wide range of biological activities, including antibacterial, antioxidant, enzymetyrosinase inhibitors, and selective oxidizing agents for the synthesis of unsymmetrical disulfide [1-2]. Several freely accessible computational tools are currently available via the Internet, based on chemical similarity assessment (ChemProt, SuperPred, SEA, SwissTargetPrediction, and TargetHunter) or machine learning methods (ChemProt and PASS), that predict versatile profiles of drug-like compounds. Among these tools, PASS (prediction of activity spectra for biologically active structures) has the highest sensitivity value [3]. For this reason, PASS was preferred in this study. Firstly, [1,3-dimethyl-5-[(2,6-dimethylphenylamino)-methylene] pyrimidine-2,4,6-trione compound was synthesized according to literature [4]. Its molecular and crystal structure was solved by the single-crystal X-ray diffraction method. The compound crystallizes in the Monoclinic crystal system and its space group is P21/n. Afterward, biological activity estimation studies were performed using PASS online software. Biological activity predictions indicate that CYP2H substrate (Pa: 0.749 and Pi: 0,026), Ubiquinol-cytochrome-c reductase inhibitor (Pa: 0,627 and Pi: 0,096), Nicotinic alpha6beta3beta4alpha5 receptor antagonist (Pa: 0,568 and Pi: 0,085), Kidney function stimulant (Pa:0.55 and Pi: 0.066) and Acylcarnitine hydrolase inhibitor (Pa: 0,524 and Pi: 0,058) activities of the compound. In addition, 14 barbiturate compounds were obtained from “CSD (Cambridge Structural Database)”, biological activity estimates were made using PASS online and the results were compared. This work was supported by “Scientific Research Project Unit (BAP) of Dokuz Eylül University” (Project No: 2019.KB.FEN.36). References [1] Stojiljković, I. N., Rančić, M. P., Marinković, A. D., Cvijetić, I. N., & Milčić, M. K. (2021). Assessing the potential of para-donor and para-acceptor substituted 5-benzylidenebarbituric acid derivatives as push–pull electronic systems: Experimental and quantum chemical study. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 253. [2] Yan, Q., Cao, R., Yi, W., Chen, Z., Wen, H., Ma, L., & Song, H. (2009). Inhibitory effects of 5-benzylidene barbiturate derivatives on mushroom tyrosinase and their antibacterial activities. European Journal of Medicinal Chemistry, 44(10), 4235–4243. [3] Murtazalieva, K. A., Druzhilovskiy, D. S., Goel, R. K., Sastry, G. N., & Poroikov, V. V. (2017). How good are publicly available web services that predict bioactivity profiles for drug repurposing?$. SAR and QSAR in Environmental Research, 28(10), 843–862. [4] Neumann, D., M., Cammarata, A., Backes, G., Palmer, G., E., & Jursic, B., S. (2014). Synthesis and antifungal activity of substituted 2,4,6-pyrimidinetrione carbaldehyde hydrazones. Bioorg. Med. Chem., 22(2), 813-826.