Multi-selective reaction of azinane bearing oxadiazoles and substituted haloalkanes catalyzed by alkali metal hydride to access anti-enzymatic agents

• Published in: Journal of Molecular Structure
• Main Author: Umair M.; Aziz-ur-Rehman; Abbasi M.A.; Siddiqui S.Z.; Iqbal J.; Rasool S.; Khan S.U.; Shah S.A.A.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85175714119&doi=10.1016%2fj.molstruc.2023.136936&partnerID=40&md5=9d6350cc30c73654da22e57ce9ff7261

The diverse biological activities of 1,3,4-oxadiazole derivatives are very significant due to structural complexity. Concentrating on metal free synthesis of 1,3,4-oxadiazole hybrids, 5a-s were obtained by two methodologies including conventional and microwave assisted. The microwave assisted synthesis was proved to be better option for selection in future due to time saving and excellent yield. 1,3,4-Oxadiazole, 3, was synthesized in three consecutive phases and finally reacted with a series of electrophiles, 4a-s, acknowledged as alkyl halide to get the anticipated compounds. Final compounds were acquired through two different routes including conventional and microwave assisted methods. IR, 1H-NMR, 13C-NMR and elemental analysis were performed for the structural elucidation of synthesized derivatives. B3LYP method and the basis set of 6-311++G (d,p) were used for natural bond orbital and structural optimization. The time-dependent density functional theory (TD-DFT) helped for the calculation of frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) at the same level of selected compounds as potential candidates against the enzymes taken into account. The screenings of all the nineteen derivatives were performed against alpha-glucosidase, urease and butyryl cholinesterase enzymes. Six compounds actively inhibited alpha-glucosidase in comparison with acarbose; four actively inhibited urease in comparison with thiourea; and five actively inhibited butyryl cholinesterase in comparison with eserine. Three compounds, 5n, 5a and 5q showed good inhibition potential and found the best in the synthesized series. © 2023