Substituted Quinazolines, Part 2. Synthesis and In‐Vitro Anticancer Evaluation of New 2‐Substituted Mercapto‐3H‐quinazoline Analogs

Abstract

A new series of 2-substituted mercapto-3H-quinozolines bearing 6-iodo and 2-heteroarylthio functions was synthesized and screened for their in vitro antitumor activity. Eighteen compounds were identified as active anticancer agents. N'-[(3-Benzyl-4-oxo-6-iodo-3H-quinazoline-2-yl)thioacetyl]-N(3)-ethylthiosemicarbazide (10), N-benzoyl-N'-[2-(3-benzyl-4-oxo-6-iodo-3H-quinozolin-2-yl)thioacetyl]hydrazine (12), and 2-[(3, 6-dioxo-pyridazin-4-yl)thio]-3-benzyl-4-oxo-6-iodo-3H-quinazoline (20) proved to be the most active members in this study. They showed MG-MID, GI(50) values of 12.8, 11.3, and 13.8 microM, respectively. The detailed synthesis and biological screening data are reported.

Synthesis of Some Pyrazolines and Pyrimidines Derived from Polymethoxy Chalcones as Anticancer and Antimicrobial Agents

“…Being a building unit of DNA and RNA, pyrimidine derivatives were found to be associated with a variety of chemotherapeutic effects including antimicrobial [21,22], antitubercular [23], antifungal [24], antiviral [25], and antitumor activities [26,27]. Furthermore, many pyrimidinethiones and their thioether derivatives were proved to exhibit potent anticancer as well as antimicrobial activities [28,29], besides being analogs of S-DABOs (dihydro-alkylthio-benzyl-oxopyrimidines) which possess antiproliferative as well as antiviral activities [30].…”

Design, synthesis and cytotoxic evaluation of novel imidazolone fused quinazolinone derivatives

“…Quinazolinone and its derivatives have drawn much attention because of their pharmacological activities particularly a wide range of antitumor activities (Khalil et al, 2003). Anilinoquinazolines in particular are potent inhibitors of growth factor receptor tyrosine kinase (GFRTK) and have found clinical applications in epidermal and vascular endothelial GFR targets (Grunwald and Hidalgo, 2003).…”

Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors

“…The substitution pattern and spatial considerations of the p-systems in regard to the quinazoline nucleus proved to be critical for DHFR inhibition. [13][14][15][16][17] In continuation to our previous efforts, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] a new series of quinazolin-4-one analogs was designed bearing 2-(1,3,4-thiadiazolylor 4-methyl-thiazolyl-)thio-functions as hydrophobic p-system regions replacing the 2-thioalkyl or 2-thioallyl function of the lead compounds D-F; and as isosters of the prototypes G-I to explore the scope and limitations of this new class of DHFR inhibitors. In addition, 6-chloro, 6-methyl, or 6,7-dimethoxy functions, representing electron donating and electron withdrawing substituents; a phenyl or benzyl group at position 3-were introduced to the quinazolin-4-one nucleus in resemblance to the leads D-I.…”

“…The synthesized compounds (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55), and 60-65) were tested for their in vitro antimicrobial activity against a panel of standard strains of the Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), the Gram-negative bacteria (Escherichia coli and Pseudomonas aeuroginosa), and the yeast-like pathogenic fungus Candida albicans. The primary screen was carried out using the agar disc-diffusion method using Müller-Hinton agar medium.…”

“…Similarly, the 2-thioxo-function of the starting materials 57-59 was reacted with 24 or 40 under the same conditions to afford 2-(5-amino-1,3,4-thiadiazol-2-yl-thio)-3-benzyl-6-substituted or 6,7-disubstituted-quinazolin-4(3H)-ones (60-62) and 2-(2-amino-4-methylthiazol-5-ylthio)-3-benzyl-6-substituted or 6,7-disubstituted-quinazolin-4(3H)-ones (63-65) respectively, Scheme 2. Structure elucidation of the synthesized intermediates and final products was attained by the aid of elementary analyses, 1 The synthesized compounds (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55), and 60-65) were evaluated as inhibitors of bovine liver DHFR using reported procedure. 37 Results were reported as IC 50 with IC 50 range of 1.0-5.0 lM, the rest of the tested compounds were considered to be inactive with IC 50 > 5 lM.…”