Chemistry, anti-diabetic activity and structural analysis of substituted dihydropyrimidine analogues

• Published in: Journal of molecular structure Vol. 1227; p. 129412
• Main Authors: Bairagi, Keshab M., Younis, Nancy Safwat, Emeka, Promise Madu, Venugopala, Katharigatta N., Alwassil, Osama I., Khalil, Hany Ezzat, Sangtani, Ekta, Gonnade, Rajesh G., Mohanlall, Viresh, Nayak, Susanta K.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-03-2021
• Subjects: Dihydropyrimidine (DHPM); Hypoglycemia; Streptozotocin (STZ); Type-2 diabetes mellitus (T2DM); Dihydropyrimidine (DHPM); Hypoglycemia; Type-2 diabetes mellitus (T2DM); Streptozotocin (STZ)
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.129412

•Synthesized a series of newly dihydropyrimidine analogues using one-pot tricomponent method.•Synthesized DHPM molecules are screened for antidiabetic activity study using in vivo rat model and some of these molecules showed promising activity.•Antidiabetic activity results are corelated with the variation of functional groups in DHPM molecule through structural analysis via single crystal study, cambridge structural database and hirshfeld surface analysis.
In an effort to identify an anti-diabetic agent, a series of methyl/ethyl 4-(hydroxyphenyl)-6-methyl-2-oxo/thioxo-1,2,3,4 tetrahydropyrimidine-5-carboxylate analogues (4a-h) have been synthesized, purified, and characterized by using Fourier-Transform Infrared Spectroscopy (FT-IR) and NMR (1H and 13C). The synthesized compounds were screened for anti-hyperglycemic activity using Streptozotocin (STZ) induced diabetic rat model. The anti-hyperglycemic activity of dihydropyrimidine (DHPM) compound is mainly analyzed with the variation of substituents present on the phenyl ring and urea/thiourea group on pharmacophoric features. Further, the crystal structure and supramolecular characteristics of two compounds 4c and 4f were analyzed through a single-crystal X-ray method and the Hirshfeld Surface Analysis, which shows hydrogen bonding through N-H···O and N-H···S interactions with the formation of ring motif in the crystal structure. It is interesting to note that among the title compounds, the 4a, 4e, 4f, and 4g significantly displayed a better hypoglycemic effect in vivo rat model study.
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