ChemInform Abstract: Synthesis and Biological Testing of 2,4‐Disubstituted Thiazole Derivatives as Potential Antitumor Antibiotics.

Abstract

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Synthesis and Biological Evaluation of Some 2,4,5‐Trisubstituted Thiazole Derivatives as Potential Antimicrobial and Anticancer Agents

“…They were found to be associated with a wide range of chemotherapeutic activities including antimicrobial [4 -7], antifungal [8,9], antiparasitic [10], and antiviral [11,12] activities. On the other hand, thiazole-containing compounds were reported to contribute to a variety of anticancer potentials including antitumor [13,14], cytotoxic [15,16], antiproliferative [17,18], DNAcleaving [19,20], and angiogenesis inhibiting [21] activities. Interest in the chemotherapeutic activity of thiazoles was potentiated after the discovery of the natural antineoplastic antibiotics tiazofurin [22,23], bleomycin, netropsin, and thiazole netropsin [24].…”

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.…”

“…Percentage growth inhibition (GI %) of in vitro subpanel tumor cell lines at 10 lM concentrations of compounds[26][27][28][29][30][31][32][33][34][35][36][37][38][39] …”