DOCKING STUDY OF CHRYSIN DERIVATIVES ON DIFFERENT TARGETS FOR ANTICANCER ACTIVITY

Some anticancer molecules using natural flavonoid chrysin were designed and docking studies were performed using Molegro Virtual Docker (MVD) software. Of the available crystal structures of the non- mutated Homo sapiens, five were selected for the final docking studies. The docking results with selected crystal structures shown that designed legends forms hydrogen bonds with at least two out of three key active site residues (Asp, Val and Lys). It also form hydrogen bonds to other active site residues, in particular Glu. The average MolDock score and the MolDock Re-rank score were obtained as -156.704 Kcal/mol and-125.649 Kcal/mol respectively. The docking results shown that some molecules fit well in the active site and interact with the residues in the active site which are crucial for their biological activity

VIRTUAL SCREENING OF HETEROCYCLIC COMPOUNDS AGAINST ANGIOTENSIN-CONVERTING ENZYME FOR POTENTIAL ANTIHYPERTENSIVE INHIBITORS

Objective: The objective of this study was to investigate the antihypertensive activity of heterocyclic compounds against angiotensin-converting enzyme (ACE) through molecular docking studies. Methods: The X-ray crystal three-dimensional (3D) structure of human ACE complexed with lisinopril (PDB ID: 1O86) was retrieved from protein databank. The two-dimensional structures of 10 selected heterocyclic compounds were drawn in ACD-Chemsketch and converted into 3D structures. The 3D structures of compounds were virtually screened in the binding pockets of ACE using FlexX docking program. Further, the chemical entities revealing the molecular electronic structures of the best docked compound (Compound-4) were explored through density functional theory studies. Results: The Compound-4 showed the highest docking score of −26.6290 kJ/mol with ACE. The Hbond and non-bonded interactions are favored by phenylalanine, leucine, and arginine. The energy gap of 1.60 eV between highest occupied molecular orbital and lowest unoccupied molecular orbitals explained the presence of strong electron-acceptor group. Furthermore, the molecular electrostatic potential studies clearly envisaged the requirement of electropositive and electronegative groups are crucial for the ACE inhibitor activities. Conclusion: The identification of good ACE inhibitors requires the understanding of the current ACE inhibitors. Thus, the docking interactions of Compound-4 and its molecular electronic structure significantly imply its potential as antihypertensive agent. However, further clinical studies are required to ascertain its potential toxic effects

Inverse QSAR approach and Molecular docking studies to design novel methoxy substituted Chalcones and their Computational Anticancer activity evaluation

Abstract Quantitative structure activity-relationship (QSAR

Antimycobacterial activity of linoleic acid and oleic acid obtained from the hexane extract of the seeds of Mesua ferrea L. and their in silico investigation

Tuberculosis is responsible for about 8 million deaths worldwide annually. The emergence of multidrug-resistant and extensively drug-resistant strains urgently requires the development of new drugs against tuberculosis. Drug discovery from plants against tuberculosis is an exciting area for exploration. In the present study, the fatty acids- linoleic and oleic acids isolated and identified from the seeds of the plant Mesua ferrea L. exhibited antimycobacterial activity. The analysis was done using Gas Chromatography-Mass Spectrometry and supplementary information was obtained using fourier transform-infra red and 1H and 13C nuclear magnetic resonance. The minimum inhibitory concentration of the purified fraction containing both the compounds was found to be 78 µg/mL. In silico molecular docking studies against the target proteins GlfT2, Inh A and mtKasB of Mycobacterium tuberculosis revealed high scores for both the compounds. Cytotoxicity studies of the compounds revealed no toxicity and high antioxidant activity was observed

In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of β-amyloid plaques associated with Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of the brain. Inhibition of acetylcholinesterase has successfully been used as a drug target to treat Alzheimer's disease but drug resistance shown by butyrylcholinesterase remains a matter of concern in treating Alzheimer's disease. Apart from the many other reasons for Alzheimer's disease, its association with the genesis of fibrils by β-amyloid plaques is closely related to the increased activity of butyrylcholinesterase. Although few data are available on the inhibition of butyrylcholinesterase, studies have shown that that butyrylcholinesterase is a genetically validated drug target and its selective inhibition reduces the formation of β-amyloid plaques.</p> <p>Rationale</p> <p>We previously reported the inhibition of cholinesterases by 2,3-dihydro-1, 5-benzothiazepines, and considered this class of compounds as promising inhibitors for the cure of Alzheimer's disease. One compound from the same series, when substituted with a hydroxy group at C-3 in ring A and 2-thienyl moiety as ring B, showed greater activity against butyrylcholinesterase than to acetylcholinesterase. To provide insight into the binding mode of this compound (Compound A), molecular docking in combination with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases.</p> <p>Conclusion</p> <p>Molecular docking studies revealed that the potential of Compound A to inhibit cholinesterases was attributable to the cumulative effects of strong hydrogen bonds, cationic-π, π-π interactions and hydrophobic interactions. A comparison of the docking results of Compound A against both cholinesterases showed that amino acid residues in different sub-sites were engaged to stabilize the docked complex. The relatively high affinity of Compound A for butyrylcholinesterase was due to the additional hydrophobic interaction between the 2-thiophene moiety of Compound A and Ile69. The involvement of one catalytic triad residue (His438) of butyrylcholinesterase with the 3'-hydroxy group on ring A increases the selectivity of Compound A. C-C bond rotation around ring A also stabilizes and enhances the interaction of Compound A with butyrylcholinesterase. Furthermore, the classical network of hydrogen bonding interactions as formed by the catalytic triad of butyrylcholinesterase is disturbed by Compound A. This study may open a new avenue for structure-based drug design for Alzheimer's disease by considering the 3D-pharmacophoric features of the complex responsible for discriminating these two closely-related cholinesterases.</p

An Empirical Study on the Influence of Genetic Operators for Molecular Docking Optimization

Evolutionary approaches to molecular docking typically use a real-value encoding with standard genetic operators. Mutation is usually based on Gaussian and Cauchy distributions whereas for crossover no special considerations are made. The choice of operators is important for an efficient algorithm for this problem. We investigate their effect by performing a locality, heritability and heuristic bias analysis. Our investigation focus on encoding properties and how the different variation operators affect them. It is important to understand the behavior and influence of these components in order to design new and more efficient evolutionary algorithms for the molecular docking problem. Results confirm that high locality is important and explain the behavior of different crossover and mutation operators. In addition, the heritability and heuristic bias study provides some insights in how the different crossover operators perform. Optimization runs in different instances of the problem support the analysis findings. The performance and behavior of the variation operators are consistent on several molecules