ONLINE COMPUTATIONAL TOOLS FOR THE PREDICTION OF TOXICITY, DRUGLIKENESS, RECEPTOR INHIBITION AND LIGAND BASED PHARMACOPHORE DETECTION OF NOVEL 2-(2-OXO-DIHYDRO-2H-INDOL-2-YLIDENE) HYDRAZINE CARBOXMIDE SCHIFF BASES

Author(s): Maddumala Sowjanya, Baratam Anupama, R. Satyavani, Koneru Poojitha and KNV Chenchu Lakshmi

Abstract: Drug discovery and development is complicated and time-consuming process. Recently, a trend towards the use of Insilico chemistry and molecular modelling for computer-aided drug design has gained significant importance. Insilico drug design skills are used in nanotechnology, molecular biology, biochemistry etc. The main benefit of the Insilico drug design is cost effective in research and development of drugs. There are wide ranges of software that are used in Insilico drug design, Grid computing, window based general PBPK/PD modelling software, PKUDDS for structure-based drug design, Molinspiration, PHARMAGIST, Chemaxon, Data warrior, O-Series, O Chem, JAVA, Perl and Python. The present study was focused to evaluate the series of building blocks with 2-(3-oxo-dihydro-2H-indol-2-ylidene) hydrazinecarboxmide Schiff bases moiety as a target molecule for anti-convulsant activity. The hypothetically developed 2-(2-oxo-dihydro-2H-indol-2-ylidene) hydrazinecarboxmide Schiff bases targets are ensured of their reliability on in silico drug designing model. The designed molecules were subjected to a preliminary study of physicochemical properties by screening their violation to Lipinski rule of five if any, predicted for their profile study by using Cheminformatics software viz. Molinspiration, O-Series, O-Chem, PharmaGist, chemaxon and data warrior. The results obtained from these tools shows all the compounds (1s-14s) follows Lipinski rule of five, bioactive scores predict were that all the compounds were moderately active towards enzyme targets (except 10s which is active) and kinase receptor (except 3s, 9s, 11s which are active). Data Warrior which was involved in toxicity predictions showed no mutagenic (except 3s), Tumorigenic (except 3s), irritant (except 3s, 6s, 7s, 8s, 11s) and reproductive effects. The designed molecules which were studied for inhibition against cytochrome p450 and its 5 subtypes model results showed that all the compounds are inhibitors of all subtypes except compounds 3s, 8s, 11s (inhibitors of CYP2D6) 3s, 8s (inhibitors of CYP2C19) 3S (inhibitors of CYP2C9) 3S-8S, 11S (inhibitors of CYP1A2) was observed for designed molecules. The pharmacophore mapping studies for anticonvulsant activity in comparison with the standard phenytoin exbhiting best pairwise alignments with a score ranging from (6.01837 for the1s, 2s, 14s & 6.3238 for 3s, 5s & 4.52 for 6s, 7s, 8s, 13s and 4.53 for 4s, 10s, 11s & 4.84 for 9s) .9.05026 for 12 with good activity. Thus, designed Schiff base derivatives might serve as the best drug lead for the existence of minimizing pathogen anti convulsant activity.

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