Discovery of potent antiproliferative agents from selected oxygen heterocycles as EGFR tyrosine kinase inhibitors from the U.S. National Cancer Institute database by in silico screening and bioactivity evaluation

Q4 · MEDICINE

Article

Author: Ruchirawat, Somsak ; Seetaha, Supaporn ; Saruengkhanphasit, Rungroj ; Niwetmarin, Worawat ; Choowongkomon, Kiattawee ; Jiwacharoenchai, Nattanan ; Eurtivong, Chatchakorn

A similarity search was conducted on the U.S. Enhanced National Cancer Institute Database Browser 2.2 to find structures related to 1,5-dihydroxy-9H-xanthen-9-one, a previously established EGFR-TK inhibitor. Compounds were virtually screened and selected for bioactivity testing revealed 5 candidates, mostly displayed stronger antiproliferative activities than erlotinib with IC₅₀ values between 0.95 and 17.71 μM against overexpressed EGFR-TK cancer cell lines: A431 and HeLa. NSC107228 displayed the strongest antiproliferative effects with IC₅₀ values of 2.84 and 0.95 μM against A431 and HeLa cancer cell lines, respectively. Three compounds, NSC81111, NSC381467 and NSC114126 inhibited EGFR-TK with IC₅₀ values between 0.15 and 30.18 nM. NSC81111 was the best inhibitor with IC₅₀ = 0.15 nM. Molecular docking analysis of the 3 compounds predicted hydrogen bonding and hydrophobic interactions with key residues were important for the bioactivities observed. Furthermore, calculations of the physicochemical properties suggest the compounds are drug-like and are potentially active orally.

01 Mar 1970·Journal of Medicinal ChemistryQ1 · MEDICINE

Preparation and the results of antitumor screening of some substituted amino-, azido-, halogeno- and hydroxy-p-benzoquinones

Q1 · MEDICINE

Article

Author: Cheng, Chia-Chung ; Zee-Cheng, Kwang-Yuen

Synthesis of some amino-, azido-, hydroxyl-, and halo-substituted p-benzoquinones are reported.The aminobenzoquinones were prepared by catalytic reduction of the corresponding azide compounds; the latter in turn were obtained by the treatment of halobenzoquinones with NaN3.Alkylaminoquinones were prepared either by the replacement of methoxyquinones with appropriate amines or by refluxing dialkyl-or diarylbenzoquinones with amines.Some alkyl analogs of 2,5-dihydroxy-3,6-diphenyl-p-benzoquinone (polyporic acid) were prepared by free-radical alkylation of 2,5-dihydroxy-p-benzoquinone with acyl peroxide.Preliminary screening results of these compounds indicated that 2,5-diazido-3,6-dimethoxy-p-benzoquinone, 2,5-dichloro-3,6-diphenyl-p-benzoquinone, and 2,5-bis(p-ethylphenyl)-3,6-dihydroxy-p-benzoquinone (I) possessed moderate activity against Walker carcinosarcoma 256.I also possessed some activity against leukemia L-1210.Marked weight loss in the surviving animals was observed.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Discovery	Thailand	Kasetsart University	04 Jan 2022

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