New Quinazoline-Sulfonylurea Conjugates: Design, Synthesis and Hypoglycemic Activity

Abstract

Background: Sulphonylureas are the oldest and commonly used to treat diabetic patients, but its efficacy declines by time. It was reported that quinazoline nucleus exhibits a potent hypoglycemic effect in diabetic animal models. Objective: The current study aimed to synthesize new quinazoline-sulfonylurea conjugates and evaluate their hypoglycemic effects in alloxan-induced diabetic rats. Methods: The conjugates were synthesized by bioisosteric replacement of 5-chloro-2-methoxybenzamide moiety in glibenclamide or 1,3-dioxo-3,4-dihydroisoquinoline moiety in gliquidone with 6,7-dimethoxy-4-oxoquinazoline moiety (compounds 4a-4d, 9b-9c and 10b-10d). Diabetes was induced in rats by a single i.p. administration of alloxan, followed by treatment with the synthesized conjugates (5mg/kg Body weight). Results: All conjugates showed hypoglycemic effects with different efficacy indicated by the reduction in blood glucose and elevation of insulin levels. Moreover, these conjugates up-regulated the expression of pancreatic glucose transporter 2, muscle glucose transporter 4, and insulin receptor substrate-1 genes, compared to the diabetic group. A normal pancreatic tissue pattern was noticed in diabetic rats treated with compounds 9b, 9c, and 10c. Conclusion: Conjugation of sulfonylurea with quinazoline (especially 9b, 9c, 10c) possessed a significant hypoglycemic effect through improving blood insulin level and insulin action and consequently increased the glucose uptake by the skeletal muscles.

PIFA Mediated Synthesis of Bis‐1,2,4‐triazoloquinazolines as Potential Anticancer Agents on MCF‐7 Cancer Cells: Characterization, Molecular Docking, Antiproliferative and ADME Profile

“…Quinazolines are the privileged nitrogen-containing heterocyclic scaffold for which the biological and pharmacological potential is well-known in the literature. [1] Recently reported bioactivities on quinazoline as a central core nucleus include anti-tubercular, [2] antimalarial, [3] anticonvulsant, [4] hypoglycemic, [5] anti-influenza, [6] anti-inflammatory (IRAK4 inhibitor), [7] anti-plasmodial, [8] analgesic, [9] antileishmanial, [10] antimicrobial, [11] anti-angiogenesis, [12] and carbonic anhydrase (CA) inhibitor. [13] Moreover, 1,2,4-triazole scaffolds are also known as important therapeutic agents for drug designing and pharmacological advancements in cancer scenario.…”

Synthesis, biological evaluation, and computational studies of some novel quinazoline derivatives as anticancer agents

“…Therefore, there is an urgent need to find novel and selective compounds as antiproliferative agents. Quinazoline scaffolds have been shown to have various biological and pharmacological effects including anti-cancer [6][7][8], anti-diabetes [9], antifungal [10], antibacterial [11,12], antihypertensive [13] and anti-tuberculosis activity [14]. In addition, there are various quinazoline scaffold based compounds in the market such as erlotinib, gefitinib (structures I and II) and structures III-VI, with high cytotoxic activity toward different cancerous cell lines (Fig.…”

2,4‐Bis(2‐(E)‐arylidenehydrazinyl)quinazolines: Expeditious Synthesis, Characterization, Antiproliferative Effects against Breast Cancer Cell Line and Molecular Docking Studies

“…[1] More interestingly, its provocative pharmacological profile is still exponentially growing through pervasive research articles and patents that have been reported during the last decades. Recently reported bioactivities on quinazoline as central core nucleus includes anti-tubercular, [2] antimalarial, [3] anticonvulsant, [4] hypoglycemic, [5] antiinfluenza, [6] anti-inflammatory (IRAK4 inhibitor), [7] antiplasmodial, [8] analgesic, [9] antileishmanial, [10] antimicrobial, [11] anti-angiogenesis [12] and carbonic anhydrase (CA) inhibitor [13] etc. The therapeutic attribute of quinazoline pharmacophore also demonstrates remarkable efficacy as a selective inhibitor of EGFR tyrosine kinase, [14] JAK2-STAT3, [15] PAK4, [16] VEGFR-2, [17] PI3K, [18] CYP1A2, [19] HDAC [20] and EGFR/HER2 [21] which plays significant roles in cancer development.…”