Design, Synthesis, In‐Vivo Anti‐Diabetic Activity, In‐Vitro α‐Glucosidase Inhibitory Activity and Molecular Docking Studies of Some Quinazolinone Derivatives

Abstract

A new series of quinazolinone bearing acetamide derivatives were designed and synthesized. The designed compounds were tested for their in vivo anti‐hyperglycemic effects against STZ‐induced hyperglycemic rats. Compound 10 a displayed the strongest hypoglycemic effect with blood glucose level reduction of 43.75 %. Besides, congeners 10 e, 10 i, 10 j, and 11 c strongly reduced the glucose level with percent reduction of 33.08, 30.00, 35.00, and 32.83 %, respectively. The most active members were then evaluated for their ability to inhibit Saccharomyces cerevisiae α‐glucosidase using BioVision α‐Glucosidase Inhibitor Screening Kit. Compounds 10 a and 11 c possessed potent α‐glucosidase inhibitory activity with IC50 values of 649 and 715 μM, respectively. Molecular docking study against the α‐glucosidase homology model was performed to understand the molecular interactions between the molecule and enzyme.

Microwave Synthesized Hydrophilic 4‐Oxo‐2‐phenylquinazoline‐3(4H)–carboximidamide and –Carboxamide as Privileged Small Molecule Scaffolds with Anti‐HIV‐1 Activities

“…They have a wide range of versatile applications that include a plethora of biological activities like anti-cancer, anti-inflammatory, antiviral, antibiotics, and many other medicinal applications. [5][6][7][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Several 2,3-disubstituted quinazolinones have been reported with antitubercular properties. [33][34] Theoretical docking has confirmed their potential as antitubercular agents in the case of several 2-methyl or 2-phenyl-substituted quinazolinones.…”

“…Though advancements toward the treatment of drug‐resistant tuberculosis strains have been significant in the last decade, [4] the need to develop drugs that may treat HIV and also address Mycobacterium tuberculosis by having both antiviral as well as antibacterial signatures specific to HIV/TB coinfections is imperative. Quinazolinones are ketonic forms of quinazolines (benzo‐fused pyrimidines) with popular relevance in pharmaceutics and medicinal chemistry [5–9] . These heterocycles are essential constituents of natural systems and are frequently found in alkaloids and many bioactive molecules [10] .…”

“…Quinazolinones are ketonic forms of quinazolines (benzo-fused pyrimidines) with popular relevance in pharmaceutics and medicinal chemistry. [5][6][7][8][9] These heterocycles are essential constituents of natural systems and are frequently found in alkaloids and many bioactive molecules. [10] The unique structure of quinazolines with two fused six-membered aromatic rings, benzene, and a pyrimidine ring, impart to it interesting properties that can be exploited in biological systems.…”

“…The presence of the benzene ring enhances the reactivity of the 3,4‐double bond, making quinazolines very reactive to incoming nucleophiles. They have a wide range of versatile applications that include a plethora of biological activities like anti‐cancer, anti‐inflammatory, antiviral, antibiotics, and many other medicinal applications [5–7,15–32] . Several 2,3‐disubstituted quinazolinones have been reported with antitubercular properties [33–34] .…”

Design, synthesis, in-silico studies and apoptotic activity of novel amide enriched 2-(1H)- quinazolinone derivatives

“…The quinazoline moiety serves as a fundamental structural unit in various physiologically active chemicals and medicinal molecules [ 18 ]. Quinazoline and quinazolinone derivatives have been attracted by biologists and medicinal chemists due to their diverse pharmacological activities [ 19 , 20 ], including anticancer [ [21] , [22] , [23] , [24] ], antitubercular [ [25] , [26] , [27] ], antimalarial [ 28 ], anti-inflammatory [ 29 , 30 ], antimicrobial [ 31 ], anticonvulsant [ 32 ], antihypertensive [ 33 , 34 ], antidiabetic [ 35 ], anti-HIV [ 36 ], antitumor [ [37] , [38] , [39] ], antioxidant [ 40 ], antiviral [ 41 ], kinase inhibitory [ 42 ], sedative-hypnotic, antihistaminic and many other uses [ 43 ]. Quinazoline and its derivatives are promising cancer chemotherapeutic agents for treating solid tumors [ [44] , [45] , [46] , [47] , [48] , [49] , [50] ].…”