Design and synthesis of novel tranilast analogs: Docking, antiproliferative evaluation and in-silico screening of TGFβR1 inhibitors was written by Ismail, Magda M. F.;El-Zahabi, Heba S. A.;Ibrahim, Rabab S.;Mehany, Ahmed B. M.. And the article was included in Bioorganic Chemistry in 2020.Recommanded Product: 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile This article mentions the following:
This work summarizes design, synthesis and biol. evaluation of sixteen novel tranilast analogs I [X = F, Cl, Br], II [X = F, O2N], [X = H, Me; R1 = OMe, Cl; R2 = H, Cl], IV [Ar = 2-thiophenyl, 2,4-dimethylphenyl, 4-pyridinyl] and V [R = cyano, ethoxycarbonyl] on different tumors such as PC-3, HepG-2 and MCF-7 cell lines. The in-vitro cytotoxicity was evaluated using MTT assay showed that, twelve compounds out of sixteen showed higher cytotoxic activities (IC50‘s 1.1-6.29μM), than that of the reference standard, 5-FU (IC50 7.53μM). The promising cytotoxic hits II [X = F], IV [Ar = 2-thiophenyl] and V [R = CN, X = 2,5-dimethoxy, n = 1; R = CN, X = OH, 2,5-dimethoxy, n = 0] proved to be selective to cancer cells when their cytotoxicity’s are examined on human normal cell line (WI-38). Then they were investigated for their possible mode of action as TGFβR1 inhibitors; remarkable inhibition of TGFβR1 by these hits was observed at the range of IC50 0.087-3.276μM. The cell cycle anal. of the most potent TGFβR1 inhibitor, II [X = O2N] revealed cell cycle arrest at G2/M phase on prostate cancer cells. Addnl., it was clearly indicated apoptosis induction at Pre-G1 phase, this was substantiated by significant increase in the expression on the tumor suppressor gene, p53 and up regulation the level of apoptosis mediator, caspase-3. In addition, in-silico study was performed for validating the physicochem. and ADME properties which revealed that, all compounds were orally bioavailable with no side effects complying with Lipinski rule. The proposed mode of action was further explored on the light of mol. modeling simulation of the most potent compounds, II [X = O2N] and V [n = 0, R = CN, X = 2,5-dimethoxy] which were docked into the active sites of TGFβR1 to predict their affinities toward the receptor. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Recommanded Product: 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile).
2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2) belongs to nitriles. Nitrile carbon shifts are in the range of 115â?25 ppm whereas in isonitriles the shifts are around 155â?65 ppm. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.Recommanded Product: 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts