title: 2-alkyl(aryl)-quinazolin-4(3H)-thiones, 2-R-(quinazolin-4(3H)-ylthio)carboxylic acids and amides: synthesis, molecular docking, antimicrobial and anticancer properties.
abstract: In this study, a series of novel 2-alkyl(aryl)-quinazolin-4(3H)-thiones, 2-R-(quinazolin-4(3H)-ylthio)carboxylic acids and amides were synthesized and evaluated for antimicrobial and anticancer activities. Their structure was confirmed by elemental analysis and spectral data (FT-IR, LC-MS, (1)H-NMR). Antimicrobial activity was tested in vitro against Staphylococcus aureus, Enterococcus faecalis, Enterobacter aerogenes, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, Candida albicans and NCI in vitro preliminary anticancer activity against nine different cancer types. The most active antibacterial and antifungal compounds were: 2.1, 2.2 and 2.4. The introduction of the carboxylic acid or amide residue into the fourth position of quinazolin-4(3H)-thione resulted in the absence of antimicrobial activity. Substance 3.8 inhibited renal cancer UO-31 line and 2.18 - leukemia CCRF-CEM. The results of in silico molecular docking for DHFR and CK2 kinase had no correlation with in vitro properties, proposing the presence of other biological activity pathways.
authors.affiliation: a Department of Organic and Bioorganic Chemistry , Zaporizhzya State Medical University , Zaporizhzhya , Ukraine .
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Antypenko
authors.affiliation: a Department of Organic and Bioorganic Chemistry , Zaporizhzya State Medical University , Zaporizhzhya , Ukraine .
authors.forename: Sergiy
authors.initials: S
authors.lastname: Kovalenko
authors.affiliation: a Department of Organic and Bioorganic Chemistry , Zaporizhzya State Medical University , Zaporizhzhya , Ukraine .
authors.forename: Yulia
authors.initials: Y
authors.lastname: Posylkina
authors.affiliation: b Enamine Ltd. , Kyiv , Ukraine .
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Nikitin
authors.affiliation: c Bacterial Laboratory, Zaporizhzhya Regional Hospital , Zaporizhzhya , Ukraine , and.
authors.forename: Natalia
authors.initials: N
authors.lastname: Fedyunina
authors.affiliation: d Department of Chemistry , Kryvyi Rih National University , Kryvyi Rih , Ukraine.
authors.forename: Vitalii
authors.initials: V
authors.lastname: Ivchuk
mesh_terms: D000577:Amides / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry; D047390:Casein Kinase II / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000577:Amides; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D013762:Tetrahydrofolate Dehydrogenase; D047390:Casein Kinase II
keywords: 2-Alkyl(aryl)-quinazolin-4(3H)-thiones; antibiotic; anticancer; antifungal; molecular docking