31374-18-2Relevant articles and documents
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Price et al.
, p. 1305 (1946)
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McKee et al.
, p. 184 (1947)
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Synthesis and Biological Evaluation of Quinazolonethiazoles as New Potential Conquerors towards Pseudomonas Aeruginosa
Wang, Jie,Battini, Narsaiah,Ansari, Mohammad Fawad,Zhou, Cheng-He
, p. 1093 - 1103 (2021/04/29)
Novel quinazolonthiazoles were designed and synthesized as new potential antimicrobial agents by facile multi-step procedure from o-aminobenzoic acids and 2-acetylthiazole. A series of biological evaluation showed that compound 7d was the most effective quinazolonethiazole with superior activity to reference drugs chloramphenicol and norfloxacin. This active molecule displayed unobvious bacterial resistance against P. aeruginosa, the low toxicity to normal hepatocytes, suitable pharmacokinetics and drug-likeness. The preliminary biological interaction suggested that quinazolonethiazole 7d might induce bacterial death by disturbing the membrane permeability, whilst preventing bacteria from growth by integrating into DNA and binding with topoisomerase IV. These findings provided significant background for the further development of quinazolonethiazoles as new potential drugs in combating drug-resistant pathogens.
In-silico Studies of the Antiproliferative Activity of New Anilinoquinazoline Derivatives Against NSCLC Cells.
Abdulwahab, Muhammad Kumayl,Ariffin, Azhar,Dzulkeflee, Rashidi,Heh, Choon Han,Leong, Kok Hoong,Tan, Ke Han
, (2020/12/28)
The current reversible epidermal growth factor (EGFR) tyrosine kinase inhibitors of non-small cell lung cancer (NSCLC) have been resisted by T790M mutation, while the irreversible inhibitors introduced to overcome the mutation have faced resistance from C979S mutation. In the effort to discover potentially improved reversible EGFR inhibitors, a series of new anilinoquinazoline derivatives with modification on the 2nd carbon on the aniline ring was synthesized. The derivatives were tested for their antiproliferative activity against NSCLC cell lines with wild-type (A549), exon 19 deletion mutated (H1650) and L858R+T790M (H1975) mutated EGFR kinases. Three derivatives (4-6) performed better than the standard drug, gefitinib, in all cell lines. Derivative 5 recorded the lowest IC50 values in all cell lines (A549: 24.60 ± 0.75 μM, H1650: 14.83 ± 0.54 μM, H1975: 21.72 ± 1.21 μM). A molecular docking study followed by molecular dynamics simulations was performed on derivative 5 and gefitinib using wild-type EGFR kinase (WT-EGFR) and L858R+T790M mutated kinase (LRTM-EGFR) to provide an understanding of their binding mechanisms. In WT-EGFR kinase, derivative 5 recorded better hydrogen bonding occupancy with MET793 (94.16%) and binding energy profile (-35.287 kcal/mol) as compared to gefitinib (91.80%, -26.071 kcal/mol). In LRTM-EGFR kinase, derivative 5 recorded better hydrogen bonding occupancy with MET793 (93.68%) as compared to gefitinib (91.48%). Derivative 5 also recorded additional hydrogen bonding interactions with ASP855, with a total of 60.61% occupancy as well as a better energy profile (-42.867 kcal/mol) as compared to gefitinib (-41.778 kcal/mol).
