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Published on:February 2019
Indian Journal of Pharmaceutical Education and Research, 2019; 53(2):276-285
Original Article | doi:10.5530/ijper.53.2.36

Identification of (1E, 3E)-1, 3-bis [(2-hydroxy- 1-naphthyl) methylene] Urea as Mutated MAP Kinase P38 Inhibitor through Reverse Pharmacophore Mapping Approach: Green Synthesis, Characterisation and in silico Docking analysis


Authors and affiliation (s):

Devika Bhai Rajamma1, Girija Chamarahalli Ramakrishna Iyer2,3*, Inamul Hasan Madar4,5, Prashantha Karunakar6

1Research and Development Centre, Bharathiar University, Coimbatore, Tamil Nadu 641046, INDIA.

2Department of Chemistry, SSMRV Degree College, Jayanagar 4th T Block, Bangalore, Karnataka 560041, INDIA.

3Department of Chemistry, Government Science College, Nrupatunga Road, Bangalore, Karnataka 560001, INDIA.

4Department of Biotechnology and Genetic Engineering, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, INDIA.

5Department of Biochemistry, Islamiah College, Vaniyambadi, 635751, Vellore, Tamil Nadu, INDIA.

6Department of Biotechnology, PES University, Bangalore, Karnataka 560085, INDIA.

Abstract:

Introduction: Investigations on Schiff bases are one of the current pharmaceutical research trends due to their broad-spectrum biological activities and unique structural features such as intramolecular hydrogen bond formation, unsaturated C-N bond, the high mobility of hydrogen-bonded proton and pseudo aromatic ring formation. Aim: Current work is an attempt to discover the therapeutic potential of such structurally related Schiff bases compounds1-[(E)-[6-[(E)-(2-hydroxy-1-naphthyl) methyleneamino]- 2-pyridyl] iminomethyl] naphthalen-2-ol; P(a), (E)-1-(2-methoxy-1-naphthyl)-N-[6- [(E)- (2-methoxy-1- naphthyl) methyleneamino]-2-pyridyl] methanimine; P(b), (E)-1- (1-naphthyl)- N-[6-[(E)-1-naphthylmethyleneamino]-2-pyridyl] methanimine; P(c) and (1E,3E)-1,3-bis [(2-hydroxy-1-naphthyl)methylene]urea; P2(a). Materials and Methods: Reverse pharmacophore approach was used to identify the Mutated MAP Kinase P38 as the potent target for these selected compounds. The molecular docking studies were performed by using the glide module of Schrödinger Software suite and the Molecular Dynamics simulations were performed by using GROMACS 5.1 with OPLS force field. The in silico ADMET studies for all the compounds were performed using the online server SwissADME. The interesting results obtained from docking, dynamic simulation and ADMET properties of P(a), P(b), P(c) and P2(a) led to the synthesis and characterisation of these compounds. Results: The docking and simulation studies showed the Schiff base P2(a) has the highest binding affinity. The ADMET profile inclusive of oral-bioavailability and physicochemical properties shown by this P2(a) proves that it is the most pertinent lead molecule for a novel drug design. Conclusion: Hence, this work identifies the potential drug-like molecule (1E, 3E)-1,3-bis[(2-hydroxy-1-naphthyl) methylene] urea; P2(a) as Mutated MAP Kinase P38 inhibitor and provides the scope of advance in vivo studies to further explore the therapeutic potential of such compounds.

Key words: Schiff bases, Reverse PharmMapper, Molecular docking, Kinase inhibitor, Dynamics simulation, ADMET Studies.

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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