Showing papers by "Senthamaraikannan Kabilan published in 2018"

Synthesis and evaluation of thiazolidinone–pyrazole conjugates as anticancer and antimicrobial agents

Abstract: Aim: To synthesize a series of new thiazolidinone–pyrazole hybrids (5a–o) and assess their anticancer (in vitro and in vivo) and antimicrobial activities. Results: The compounds 5h (against Ehrlich ascites carcinoma cells), 5e and 5i (against the human breast cancer [MDA-MB231] cell line) exhibited potent anticancer activity. All the compounds except 5g and 5e found to be less toxic for the human dermal fibroblast cells. The effective interactions of the compounds in silico with MDM2 exemplified their inhibitory potency. The derivatives also showed moderate antimicrobial activity. Conclusion: The halogen atoms on various positions of the N-arylamino ring played an advantageous role in elevating the potency of the molecules. Thus, these conjugates could be used as a lead for further optimization to achieve promising therapeutics.

In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha.

Abstract: Background Breast cancer is one of the most common cancers diagnosed among women. It is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha (ERα) correlates with better prognosis and the likelihood of response to hormonal therapy. ERα is an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not exhibit any high toxic effects against normal cells. Objectives To identify the potential natural inhibitors for BCa through an optimised in silico approach. Methods Structural modification and molecular docking-based screening approaches were imposed to identify the novel natural compounds by using Schrodinger (Maestro 9.5). The Qikprop v3.5 was used for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the compounds was evaluated by MTT assay against MCF-7 Cell lines. Results From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin, Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1 respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 ± 4.0 and 58.3 ± 4.4 µM, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. Conclusion We mainly focused on in silico study to dock the compounds into the human estrogen receptor ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens. Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell line. These findings may provide basic information for the development of anti-breast cancer agents.

Crystal structures of 3-meth-oxy-4-{[5-(4-meth-oxy-phen-yl)-1,3,4-oxa-diazol-2-yl]meth-oxy}benzo-nitrile and N-(4-{[5-(4-chloro-phen-yl)-1,3,4-oxa-diazol-2-yl]meth-oxy}phen-yl)acetamide.

Abstract: The title compounds, C18H15N3O4 and C17H14ClN3O3, are heterocyclic 1,3,4-oxa­diazole derivatives which differ from each other in the groups attached to the carbon atoms: a meth­oxy­phenyl ring and a benzo­nitrile group in (I) and a chloro­phenyl ring and an acetamide group in (II). Short intra­molecular C—H⋯O hydrogen bonds occur in both mol­ecules. The crystal structure of (I) features C—H⋯N hydrogen bonds, while in the crystal structure of (II), N—H⋯N, C—H⋯N and C—H⋯O hydrogen bonds are observed.