Synthesis and Biological Evaluation of a Series of Quinoline‐Based Quinazolinones and Carbamic Anhydride Derivatives

Abstract

Quinoline-based compounds are one of the most important classes of N-heterocyclics exhibiting a wide spectrum of biological activities. There is a constant demand for the synthesis of new quinoline-based molecules suitable for therapeutic applications. Here a new strategy is developed to synthesize different quinoline-based quinazolinones catalytically using InCl 3 through a cyclocondensation reaction of isatoic anhydride and aniline with 2-substituted-quinoline-3-carbaldehyde to produce 2-(2-phenoxyquinolin-3-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one derivatives (> 90 % yields). In contrast, the reduced electrophilicity at the metal center allows the hydrazide ligand to bind In(III) and serendipitously forms benzoic(2-phenoxyquinoline-3-carbonyl) carbamic anhydride (∼ 70 % yields). The mechanistic aspects of these reactions were rationally explained. The structure and purity of all the isolated derivatives were assessed by spectroscopic and analytical data. In view of a strong correlation existing between inflammation and cancer progression, the ex-vivo anti-inflammatory effect of the ligands was established. The anti-cancer property of the proposed ligand was delineated with a specific SIRT protein family. Further, the computational docking studies on the binding abilities of 22 synthesized compounds with the Sirt1 protein were discussed in detail.

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

“…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.…”

“…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] .…”

“…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.…”

“…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] .…”

Synthesis, Structural Elucidation, In Silico and In Vitro Studies of New Class of Methylenedioxyphenyl-Based Amide Derivatives as Potential Myeloperoxidase Inhibitors for Cardiovascular Protection

“…The established method from scientific literature was followed for in vitro antioxidant, ex vivo anti-inflammatory, and in vitro α-GD, DPP-4, and MPO enzymatic inhibition studies. − Ascorbic acid and aceclofenac were used as positive controls for antioxidant and anti-inflammatory studies, respectively. For α-GD, DPP-4, and MPO enzymatic inhibition studies, acarbose, sitagliptin, and salicylhydroxamic acid were used as positive controls, respectively.…”