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

DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents

“…From a structural point of view, classical antifolates are analogs of folate containing a pterin ring, an aromatic ring, and a glutamate tail. They do not passively diffuse across cell membranes because they possess a charged glutamate tail, so they are actively transported through the reduced folate carrier system [25,34]. Non-classical antifolates are lipophilic molecules which do not need folate transport systems and passively diffuse into cells.…”

“…Docking studies (the complex hDHFR-NADPH-methotrexate was used, PDB ID: 1DLS) revealed that the amino acids Glu30, Phe31, and Phe34 are crucial for the binding interaction with the synthesized compounds. Moreover, in silico ADMET prediction studies suggested that compound 10 could be used as oral absorbing agents with a reduced toxicity [34]. In the same year, Chen et al prepared a new series of pyrrolo[3,2- f ]quinazoline, and all compounds were tested for their anti-breast cancer activity.…”

Recent advances in the pharmacological diversification of quinazoline/quinazolinone hybrids

“…In the search for potent DHFR inhibitors, Paul et al have modied existing quinazolinone-based DHFR inhibitors (12-14) [29][30][31] with the aim of increasing the hydrophobic p-interaction found to be superior in DHFR inhibition with an IC 50 of 0.011 mM, as compared with methotrexate (IC 50 of 0.02 mM). From the SAR study, it was found that the phenyl ring is essential at 2 nd position of quinazolinone for effective DHFR inhibition.…”

Synthesis, Cytotoxic, and Antibacterial Evaluation of Quinazolinone Derivatives with Substituted Amino Moiety

“…[5] These compounds shows a variety of biological activities, [6] [7] such as anticancer, [8 -13] anti-inflammatory, [14 -16] anticonvulsant, [17 -20] and antimicrobial. [21] Because of the significant biological activities of these compounds in the pharmaceutical industry, the synthesis of quinazolinone and its derivatives have aroused considerable interests of pharmaceutical researchers.…”

“…Quinazolinone is a core skeleton in a variety of natural products and synthesized compounds: febrifugine, Echinops echinatus , Bouchardatia neurococca , 3‐benzyl‐6‐((3,4‐dimethoxybenzyl)(methyl)amino)‐2‐(methylthio)quinazolin‐4(3 H )‐one, ( E )‐3‐(3‐carboxyphenyl)‐2‐(4‐ethynylstyryl)quinazolin‐4(3 H )‐one etc . These compounds shows a variety of biological activities, such as anticancer, anti‐inflammatory, anticonvulsant, and antimicrobial . Because of the significant biological activities of these compounds in the pharmaceutical industry, the synthesis of quinazolinone and its derivatives have aroused considerable interests of pharmaceutical researchers.…”