Karthik Kumara

Ethyl 3-methyl-1-phenyl-5-(p-tolyl)-1H-pyrazole-4-carboxylate

In the title compound, C20H20N2O2, the pyrazole ring makes dihedral angles of 39.74 (8) and 60.35 (8)° with the phenyl and toluene rings, respectively. The dihedral angle between the phenyl and toluene rings is 62.01 (7)°.

Design and Amberlyst-15 mediated synthesis of novel thienyl-pyrazole carboxamides that potently inhibit Phospholipase A2 by binding to an allosteric site on the enzyme

Inflammation-mediated disorders are on the rise and hence, there is an urgent need for the design and synthesis of new anti-inflammatory drugs with higher affinity and specificity for their potential targets. The current study presents an effective and new protocol for the synthesis of thienyl-pyrazoles through 3 + 2 annulations using a recyclable heterogeneous catalyst Amberlyst-15. Chalcones 3(a-g) prepared from 3-methylthiophene-2-carbaldehyde and acetophenones by Claisen-Schmidt approach reacted with semicarbazide hydrochloride 4 in the presence of Amberlyst-15 in acetonitrile at room temperature producing thienyl-pyrazole carboxamides 5(a-h) in good yields. Alternatively, the compounds 5(a-h) were prepared by conventional method using acetic acid (30%) medium. Structures of synthesized new pyrazoles were confirmed by spectral and crystallographic studies. All the new compounds were evaluated for their in vitro inhibition of Phospholipase A2 from Vipera russelli and preliminary studies revealed that, amongst the designed series, compounds 5b, 5c and 5h showed promising inhibition. Further, the compounds exhibited linear mixed-type inhibition behavior for the sPLA2 enzyme indicating that they bind to an allosteric site distinct from either the calcium or substrate binding site on the enzyme. These kinetic conclusions were further validated by macromolecular rigid-body docking whereby compounds 5c and 5h showed binding to distinct pockets on the protein. These findings present a promising series of lead molecules that can serve as prototypes for the treatment of inflammatory related disorders.

CCDC 1544183: Experimental Crystal Structure Determination

Related Article: Avinash Kotian, Karthik Kumara, Vinayak Kamat, Krishna Naik, Dhoolesh G. Kokare, Anupama Nevrekar, Neratur Krishnappagowda Lokanath, Vidyanand K. Revankar|2018|J.Mol.Struct.|1156|115|doi:10.1016/j.molstruc.2017.11.098

Crystal structure of SAM-dependent methyltransferase from Pyrococcus horikoshii

Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Å using X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II). The cofactor (SAM) molecule binds at the interface between adjacent subunits, presumably near to the active site(s) of the enzyme. The observed dimeric state might be important for the catalytic function of the enzyme.