MOLECULAR DOCKING STUDIES ON FLAVONOID COMPOUNDS: AN INSIGHT INTO AROMATASE INHIBITORS

Objective: Aromatase is a key enzyme that plays a crucial role in the synthesis of estrogen and has a major effect in pathogenesis of estrogen‑dependent disease, including breast cancer, endometrial cancer, and endometriosis. The abnormal over expression of aromatase can be inhibited by aromatase inhibitors. The objective of the present study is to evaluate the binding interaction of flavonoid compounds with cytochrome P450 enzyme aromatase, which is involved in the metabolism of estrogens and considered as a powerful target for treatment of estrogen-dependent breast cancers. Methods: To understand the mechanisms involved in the binding of flavonoid compounds and their interactions with the binding site of aromatase, molecular docking studies were carried using Autodock 4.2. Results: The docking results revealed that, benzoflavanones showed higher binding affinity compared to other class of compounds. The presence of hydrogen bond interaction and cation–π interaction contributed to their higher binding affinity. The flavonoid compounds with unsubstituted or less substituted rings showed higher binding affinity than those with substituted rings. The hydrogen bonding interactions were predominant in all the classes of compounds considered for the study and were found to be important for inhibition. The docking studies showed that the binding energies mainly depend on aromatic properties like cation–π and π–π interactions. These properties play a key role in determining the biological activity of flavonoid compounds. Conclusion: The present findings provided valuable information on the binding process of flavonoid compounds to the binding site of aromatase and revealed the structural requirement needed for binding

IN SILICO ANALYSIS OF INTERACTIONS IN HEME BINDING PROTEINS

Objective: Heme cofactors are essential molecule found in almost all forms of life. Biological systems depend on heme-protein interactions to carry out basic functions required for their survival. The objective of the present work is to analyse the various non-covalent interactions and also focus on amino acid preferences in heme binding environment.Methods: Various interactions like hydrophobic, aromatic and hydrogen bonds between heme and binding site of non-redundant dataset of 33 heme proteins were analysed to understand the characteristics of different type of interactions. Also the relative preference of amino acids participating in forming secondary structure, solvent accessibility, stabilizing residues and ion-pairs in heme binding environment was analysed.Results: The analysis of heme binding protein environment revealed some important findings, which include the dominant role of non-polar contacts. 12% of the predicted stabilizing residues were also involved in forming interaction with heme. The secondary structure preference analysis showed that 41% of interacting residues preferred to be in helix. The frequency of non-polar amino acids in the buried region was predominant. The preference of amino acid Arg to form complete ion-pair was higher and these ion-pairs formed strong interactions. This provides insights into the better understanding of the heme environment.Conclusion: The present findings through in silico analysis provide valuable information on natural heme binding proteins. These studies will contribute useful information regarding structural stability and its interaction in future designs of novel heme proteins.Â

Antidiabetic Studies of Dihydropyrimido[4,5-a]acridin-2-amines

An in vitro antidiabetic activity on -amylase and -glucosidase activity of novel 10-chloro-4-(2-chlorophenyl)-12-phenyl-5,6-dihydropyrimido[4,5-a]acridin-2-amines (3a-3f) were evaluated. Structures of the synthesized molecules were studied by FT-IR, 1 H NMR, 13 C NMR, EI-MS, and single crystal X-ray structural analysis data. An in silico molecular docking was performed on synthesized molecules (3a-3f). Overall studies indicate that compound 3e is a promising compound leading to the development of selective inhibition of -amylase and -glucosidase