Lalitha Simon

In Silico Drug-Designing Studies on Flavanoids as Anticolon Cancer Agents: Pharmacophore Mapping, Molecular Docking, and Monte Carlo Method-Based QSAR Modeling

In silico molecular modeling studies were carried out on some newly synthesized flavanoid analogues. Search for potential targets for these compounds was performed using pharmacophore-mapping algorithm employing inverse screening of some representative compounds to a large set of pharmacophore models constructed from human target proteins. Further, molecular docking studies were carried out to assess binding affinity of these compounds to proteins mediating tumor growth. In vitro anticancer studies were carried out on colon cancer cell lines (HCT116) to assess validity of this approach for target identification of the new compounds. Further important structural features of compounds for anticolon cancer activity were assessed using Monte Carlo-based SMILES and hydrogen graph-Based QSAR studies. In conclusion this study have depicted successful and stepwise application of pharmacophore mapping, molecular docking, and QSAR studies in target identification and lead optimization of flavonoids.

3-(3,4-Dimeth-oxy-benz-yl)chroman-4-one.

In the title compound, C18H18O4, the six-membered chroman-4-one ring adopts an envelope conformation with the C atom bonded to the bridging CH2 atom as the flap. The dihedral angle between the mean plane of the fused pyranone ring and the dimethoxy-substituted benzene ring is 89.72 (2)°. In the crystal, adjacent molecules are linked via C—H⋯π interactions.

rac-3-(4-Hy-droxy-benz-yl)chroman-4-one.

In the racemic title compound, C16H14O3, the ring of the 4-hydroxybenzyl substituent group forms a dihedral angle of 80.12 (12)° with the benzene ring of the chromanone system. Two C atoms of the pyranone ring and the H atoms on the benzyl α-C atom are disordered over two sites, with site-occupation factors of 0.818 (8) and 0.182 (8). The crystal structure is stabilized by O—H⋯O hydrogen bonds, which form parallel one-dimensional zigzag chains down the c axis and are interconnected by both methine C—H⋯O hydrogen bonds and weak aromatic C—H⋯π interactions, giving a sheet structure lying parallel to [011].

Synthesis, anticancer, structural, and computational docking studies of 3-benzylchroman-4-one derivatives

A series of 3-Benzylchroman-4-ones were synthesized and screened for anticancer activity by MTT assay. The compounds were evaluated against two cancerous cell lines BT549 (human breast carcinoma), HeLa (human cervical carcinoma), and one noncancerous cell line vero (normal kidney epithelial cells). 3b was found to be the most active molecule against BT549 cells (IC50 = 20.1 µM) and 3h against HeLa cells (IC50 = 20.45 µM). 3b also exhibited moderate activity against HeLa cells (IC50 = 42.8 µM). The molecular structures of 3h and 3i were solved by single crystal X-ray crystallographic technique. Additionally, the molecular docking studies between the tumour suppressor protein p53 with the lead compound 3h, which exhibited better anticancer activity against HeLa cells was examined.