Synthesis and Cytotoxic Activity against K562 and MCF7 Cell Lines of SomeN-(5-Arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazoline-2-yl)thio)acetamide Compounds

Abstract

Ethyl 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetate (3) which was synthesized starting from anthranilic acid (1) via 2-thioxo-3-phenylquinazolin-4(3H)-one (2) reacted with hydrazine hydrate to afford 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide (4). Reaction of (4) with thiocarbonyl-bis-thioglycolic acid gave a new compound name N-(4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide (5). Knoevenagel condensation of (5) with appropriate aldehydes gave fourteen (Z)-N-(5-arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide compounds (6a–o) with moderate yield. The chemical structure of the compounds was elucidated on the basis of IR, 1H-NMR, 13C-NMR, and HR-MS spectral data. The 5-arylidene-2-thioxothiazolidinone compounds exhibited mild-to-moderate cytotoxic activity against both K562 (chronic myelogenous leukemia) cells and MCF7 (breast cancer) cells.

Synthesis and structure of ethyl 2-[(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)sulfanyl]acetate

“…As shown in Fig. 1, 2-mercapto-3-phenylquinazolin-4(3H)one (3) was obtained by the reaction of anthranilic acid (1) and phenyl isothiocyanate (2) (Nguyen et al, 2019). The IR spectrum of (3) shows the stretching vibrations of N-H (3217 and 3134 cm À1 ) and C O (1659 cm À1 ) bonds, indicating that (3) exists in the thione form (Al-Majidi & Al-Khuzaie, 2015).…”

“…Hybrid derivatives, where quinazolin-4-one is incorporated with different heterocycles, possess a variety of biological effects including anticancer (Khalil et al, 2003;Gursoy & Karal, 2003;Gawad et al, 2010;Elfekki et al, 2014;El-Sayed et al, 2017;Nguyen et al, 2019), anticonvulsant (El-Azab et al, 2013) and antimicrobial (Pandey et al, 2009;Al-Khuzaie & Al-Majidi, 2014;Al-Majidi & Al-Khuzaie, 2015;Lv et al, 2018;Godhani et al, 2016) activities. Some derivatives of 2-mercapto-3-(4-methoxyphenyl)quinazolin-4(3H)-one containing the thiazolidine-4-one moiety have been found to have good antituberculosis activity (Godhani et al, 2016).…”

“…The synthetic protocol for title compound (4) is shown in Fig. 1 (Nguyen et al, 2019). Synthesis of 2-mercapto-3-phenylquinazolin-4-one (3): Phenyl isothiocyanate (2) (0.1 mol) was added to the solution of anthranilic acid (1) (0.1 mol) and triethylamine (3.0 mL) in absolute ethanol (200 mL).…”

Anticancer Profile of Rhodanines: Structure–Activity Relationship (SAR) and Molecular Targets—A Review

“…Nguyen et al synthesized a series of new structures, N-(4-oxo-2-thioxothiazolidin-3yl)-2-[(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio]acetamide derivatives, and evaluated them for their cytotoxicity potential against K562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) tumor cell lines. Compound 1 with the 2-thioxothiazolidin-4-one ring containing the active methylene group (Figure 1), as shown below, exerted moderate cytotoxicity against MCF-7 cells with a % inhibition of cell growth of 64.4% at the concentration of 100 µ g/mL [25]. On the other hand, the introduction of small groups such as -CH2COOH, -CH(CH3)COOH in the N-3 position of the rhodanine ring resulted in the formation of the N-substituted compounds 2 and 3, respectively (Figure 2).…”

Synthesis, Crystal Structures, Lipophilic Properties and Antimicrobial Activity of 5-Pyridylmethylidene-3-rhodanine-carboxyalkyl Acids Derivatives

“…Compounds containing the 2-sulfanylidene-1,3-thiazolidin-4-one core (rhodanine), the synthesis of which was first carried out by Nencki almost 150 years ago [1], have interesting biological properties and therefore are still of interest to researchers in the field of medicinal chemistry [2][3][4]. Such derivatives reveal, inter alia, antibacterial [5,6], antifungal [7,8], antiviral [9,10], antitumor [11][12][13][14], anti-inflammatory [15] and anthelmintic [16] activities. Other, non-medical applications of rhodanine derivatives are also known.…”