Anti-HIV, Antitubercular and Antibacterial Activities of Novel 3-(Substituted Quinazolinylamino)-2-phenyl quinazolin-4(3H)ones

Abstract

In the present study, we have synthesized a series of novel 2-phenyl-3-(substituted quinazolinylamino)quinazolin-4(3H)-ones by the reaction of 3-(substituted)-2-hydrazinoquinazoline-4(3H)-ones with 2-phenyl-3,1-benzoxazin-4-one. The starting material 3-(substituted)-2-hydrazinoquinazolin-4(3H)-ones were synthesized from various primary amines. All the synthesized compounds were screened for their antitubercular, anti-HIV and antibacterial activity against different Grampositive and Gram-negative strains by agar dilution method. Among the test compounds, 3-(4-nitrophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one (BQZ6) and 3-(4-chlorophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one (BQZ7) shown most potent antibacterial activity against E. coli, P. aeruginosa and S. aureus with the MIC of 3 μg/mL. The compound BQZ7 exhibited the antitubercular activity with the MIC of 25 μg/mL and anti-HIV activity with the MIC of 35.4 μg/mL against HIV1 and HIV2 and offers potential lead for further optimization and development to new antitubercular and anti-HIV agents. The results from this study confirm that the synthesized and biologically evaluated quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities and are new scaffolds for antimicrobial activity

Green synthesis of 2‐thioxo‐4‐quinazolinones from 2‐aminobenzamide and isothiocyanates

“…27 Due to their importance, many other synthetic routes have been explored for the synthesis of these 2-thioxo-4quinazolinone compounds, 28 of which the most common methods are through condensation of anthranilic acid, the ester of anthranilic acid, and 2-nitrobenzamides with isothiocyanates. 27,[29][30][31] The reaction of isatoic © 2024 Vietnam Academy of Science and Technology and Wiley-VCH GmbH.…”

“…Due to their importance, many other synthetic routes have been explored for the synthesis of these 2‐thioxo‐4‐quinazolinone compounds, 28 of which the most common methods are through condensation of anthranilic acid, the ester of anthranilic acid, and 2‐nitrobenzamides with isothiocyanates 27,29–31 . The reaction of isatoic anhydride with amines and subsequent addition of carbon disulfide, 9,32 one‐pot multicomponent synthesis of methyl 2‐bromobenzoate, phenylisothiocyanate catalyzed by CuBr, 33 some special catalysts such as NiFe 2 O 4 @SiO 2 –PPA, 34 H 3 [PW 12 O 40 ], 35 magnetic Fe 3 O 4 nanoparticles 36 have also been developed for the synthesis of 2‐thioxo‐4‐quinazolinones (See Scheme 1).…”

Green Synthesis of 2‐Thioxo‐4‐quinazolinone Derivatives in Water

“…2-Thixo-4-quinazolinones display a wide range of biological interests such as potential anti-melanogenesis agents with a tyrosinase inhibitory activity, [1] EGFR inhibitors, [2] anti-HIV, [3] antitubercular and antibacterial activities, [4] VEGFR-2 inhibitors with potential activity against the hepatocellular carcinoma, [5] anti-cancer, [6] HSP90 Inhibitors towards breast cancer targeting, [7] and dual and selective inhibitors of dynaminrelated protein 1 (Drp1) and puromycin-sensitive aminopeptidase (PSA) (Figure 1). [9] Therefore, several synthetic methods for 2-thixo-4-quinazolinones have been developed to date (Scheme 1), which include the reaction of an isatoic anhydride and amine followed by treating with carbon disulfide (Scheme 1, eq.…”

“…1), [1] condensation of anthranilic acid, anthranilic acid ester, and/or 2-aminobenzamide with isothiocyanate (Scheme 1, eq. 2), [2][3][4] Cu-catalyzed one-pot synthesis (Scheme 1, eq. 3), [8] and condensation of methyl 2-isothiocyanatobenzoate and aniline (Scheme 1, eq.…”