- Anti-HIV and Antibacterial Activities of Novel 2-(3-Substituted-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-diones
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Abstract: In the present study, we have synthesized a series of novel 2-(3-substituted-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-diones by the reaction of 3-(substituted)-2-hydrazino-quinazoline-4(3H)-ones with phthalic anhydride. The starting material 3-(substituted)-2-hydrazino-quinazolin-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 gram positive and gram negative strains by agar dilution method. Among the test compounds, 2-(3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-dione (QCT7) shown most potent antibacterial activity against E. coli, and S. aureus with the MIC of 3 μg/mL. The compound QCT7 exhibited the antitubercular activity with the MIC of 25 μg/mL and anti-HIV activity with the EC50 of 43.68 μM against HIV1 and HIV2 and offers potential lead for further optimization and development to new antitubercular and anti-HIV agents. The results obtained 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.
- Sulthana,Chitra,Alagarsamy,Saravanan,Solomon, V. Raja
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p. 112 - 121
(2021/04/05)
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- Anti-HIV, Antitubercular and Antibacterial Activities of Novel 3-(Substituted Quinazolinylamino)-2-phenyl quinazolin-4(3H)ones
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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-hydrazino-quinazolin-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 Gram-positive 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.
- Sulthana,Chitra,Alagarsamy
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p. 281 - 286
(2020/01/08)
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- Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1
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As a mitotic-specific target widely deregulated in various human cancers, polo-like kinase 1 (Plk1) has been extensively explored for anticancer activity and drug discovery. Although multiple catalytic domain inhibitors were tested in preclinical and clinical studies, their efficacies are limited by dose-limiting cytotoxicity, mainly from off-target cross reactivity. The C-terminal noncatalytic polo-box domain (PBD) of Plk1 has emerged as an attractive target for generating new protein-protein interaction inhibitors. Here, we identified a 1-thioxo-2,4-dihydro-[1,2,4]triazolo[4,3-a]quinazolin-5(1H)-one scaffold that efficiently inhibits Plk1 PBD but not its related Plk2 and Plk3 PBDs. Structure-activity relationship studies led to multiple inhibitors having ≥10-fold higher inhibitory activity than the previously characterized Plk1 PBD-specific phosphopeptide, PLHSpT (Kd ~450 nM). In addition, S-methyl prodrugs effectively inhibited mitotic progression and cell proliferation and their metabolic stability was determined. These data describe a novel class of small-molecule inhibitors that offer a promising avenue for future drug discovery against Plk1-addicted cancers.
- Alverez, Celeste N.,Park, Jung-Eun,Toti, Kiran S.,Xia, Yangliu,Krausz, Kristopher W.,Rai, Ganesha,Bang, Jeong K.,Gonzalez, Frank J.,Jacobson, Kenneth A.,Lee, Kyung S.
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p. 14087 - 14117
(2020/11/30)
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- Synthesis of new 2-(N'-Allylidene-hydrazino)quinazolinones and 2-(4,5-Dihydropyrazolyl)-quinazolinones and their antimicrobial and antifungal activity screening
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Novel 2-[N'-(1,3-disubstituted-phenyl)allylidene]hydrazine-3-ethyl-3H- quinazolin-4-one (8) and 2-(3,5-disubstituted-phenyl-4,5-dihydropyrazol- 1-yl)-3-ethyl-3H-quinazolin-4-one (9) compounds have been prepared and tested for antibacterial and antifungal activities. 1H NMR, 13C NMR, elemental analysis and mass spectroscopy methods have been used to identify molecular structures of the newly synthesized compounds. For screening antibacterial and antifungal activities of the new compounds, minimum inhibitory concentration (MIC) values were evaluated against the Staphylococcus aureus, Escherichia. coli, Pseudomonas aeruginosa, Enterococcus faecalis, Candida albicans, Candida parapsilosis and Candida krusei using microdilution broth method. Compounds 8a-8h exhibited the best antibacterial activity against E. faecalis.
- Saygili, Nezire,Ekizoglu, Melike,Erdogdu, Ceren
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p. 3197 - 3203
(2014/07/22)
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