In silico ADME-Toxicity Profiling, Prediction of Bioactivity and CNS Penetrating Properties of some Newer Resveratrol Analogues
Supriyo Saha, Mrityunjoy Acharya · 2014
In silico ADME Toxicity profiling showed an interesting results against the resveratrol and its designed ligands (D1-D16), that these ligands were permeable by intestinal (Human Colonic Carcioma Cell Line) CaCo2 cell line and D8, D9, D11, D13, D14, D15, D16 were inhibitor of CYP2C19 microsomal enzyme which were may be active against breast cancer cell line, as the D13, D16 were belong to the p- glycoprotein substrate so there was a chance of efflux in the case of absorption. As well as the toxicity profile checked against the estrogen and androgen receptor, mutagenicity, carcinogenicity, human ether a gogo cell line, LD value clarifies the basic picture of potency. As the detail mechanism of 50 resveratrol was not revealed, so the bioactivity profiling navigate the mechanism behind activity and finally the polar surface area, Log PS and Log BB value justify that molecule D1 was the better molecule which can cross the blood brain barrier. As well as there is a good correlation occurred 2 in between Log P and Log PS with the r value 0.7104 which can correlate with the brain penetration capacity of a molecule. 1 properties. There were some previous development occurred with the insertion of hydroxyl group with the phenyl group, insertion of hydroxymethyl group along with the azo stilbene , insertion of diethyl stilbene group as well as fewer derivatives with fluorine, para hydroxy phenyl, insertion of dimethyl amino groups with diversified activity 2-5 against COX-1, COX-2 and NFK-â inhibitor. Resveratrol has been found to inhibit the proliferation of several kinds of tumors such as 6-10 leukemia, prostate, breast and colon cancers. In preclinical study Sheng-Hong Tseng et al suggest that resveratrol could suppresses the 11 growth of gliomas in rat. In present study we have designed some Resveratrol analogue on basis of their physicochemical parameter and predict that weather these could target brain tumor like glioma. Due to its diversified activity profile this molecule draw the attention of the researcher to develop its newer analogue. So in this present study, our main intention is to develop a series of in silico resveratrol analogue which has a potentiality to fulfil the basic requirements for the scientists to minimize the burden of synthesis and represent a better molecule in all aspects. As we know the basic properties to justify molecular structure was its structure and electronic configuration which was directly related with the absorption profile of a molecule such as cytochrome P450 microsomal enzyme adaptivity as inhibitor or non inhibitor, Log P CaCO2 cell permeability, calculate its drug like app property as Lipinski's rule of five as well as the bioactivity prediction as these molecules were associated with enzyme/ G-protein coupled receptor or ion/nuclear receptor and calculate toxicity parameter which justify the nature of the designed ligands. The other parameter as blood brain barrier penetration capacity was determined by using value of topological polar surface area, passive permeability factor (Log PS), partition coefficient value (Log P) and Log D, where Log D means distribution constant for any ionisable compounds as a function of pH. 2.Materials and Methods 2.1. Structural modification