Xu, Biao published the artcileSynthesis, biological evaluation and structure-activity relationship of novel dichloroacetophenones targeting pyruvate dehydrogenase kinases with potent anticancer activity, Related Products of catalysis-chemistry, the publication is European Journal of Medicinal Chemistry (2021), 113225, database is CAplus and MEDLINE.
Pyruvate dehydrogenase kinases (PDKs) are promising therapeutic targets that have received increasing attentions in cancer metabolism In this paper, synthesis and biol. evaluation of a series of novel dichloroacetophenones I (R1 = cyclopropylamine, piperidin-1-yl, phenylamino, etc.) as potent PDKs inhibitors is reported. Structure-activity relationship anal. enabled to identify a potent compound II, which inhibited PDKs with an EC50 value of 0.09¦ÌM, and reduced various cancer cells proliferation with IC50 values ranging from 1.1 to 3.8¦ÌM, while show weak effect against non-cancerous L02 cell (IC50 > 10¦ÌM). In the A375 xenograft model, II displayed an obvious antitumor activity at a dose of 5 mg/kg, but with no neg. effect to the mice weight Mol. docking suggested that II formed direct hydrogen bond interactions with Ser75 and Gln61 in PDK1, and meanwhile the aniline skeleton in II was sandwiched by the conserved hydrophobic residues Phe78 and Phe65, which contribute to the biochem. activity improvement. Moreover, II induced A375 cell apoptosis and cell arrest in G1 phase, and inhibited cancer cell migration. In addition, II altered glucose metabolic pathway in A375 cell by decreasing lactate formation and increasing ROS production and OCR consumption, which could serve as a potential modulator to reprogram the glycolysis pathway in cancer cell.
European Journal of Medicinal Chemistry published new progress about 104-03-0. 104-03-0 belongs to catalysis-chemistry, auxiliary class Nitro Compound,Carboxylic acid,Benzene, name is 4-Nitrophenylacetic acid, and the molecular formula is C9H21NO3, Related Products of catalysis-chemistry.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia