77869-10-4Relevant academic research and scientific papers
Amberlyst-15 catalyzed synthesis of novel thiophene–pyrazoline derivatives: spectral and crystallographic characterization and anti-inflammatory and antimicrobial evaluation
Prabhudeva, Malledevarapura Gurumurthy,Kumara, Karthik,Dileep Kumar, Achutha,Ningappa, Mylarappa B.,Lokanath, Neratur K.,Ajay Kumar, Kariyappa
, p. 6453 - 6468 (2018)
Increasing instances of antimicrobial drug resistance and Inflammation-mediated disorders requires the design and synthesis of new small-molecules with higher affinity and specificity for their potential targets to serve as antibiotics or anti-inflammatory drugs, respectively. The current study presents the synthesis of a series of chalcones, 3(a–h) by the reaction of 3-methylthiophene-2-carbaldehyde, 1 and acetophenones, 2(a–h) by Claisen–Schmidt approach. The chalcones were efficiently transformed into thienyl-pyrazolines, 5(a–h) by their reaction with thiosemicarbazide hydrochloride, 4 in the presence of Amberlyst-15 as a catalyst in acetonitrile at room temperature. Alternatively, the compounds 5(a–h) were prepared by conventional method using acetic acid (40%) medium. Structures were characterized by spectral and single crystal X-ray diffraction studies. Preliminary assessment of the anti-inflammatory properties of the compounds showed that, amongst the series, compounds 5b and 5c have excellent anti-inflammatory activities. Further, compound 5c showed excellent activity against Escherichia coli (MIC, 15?μg/mL), Bacillus subtilis (MIC, 20?μg/mL), Aspergillus niger (MIC, 20?μg/mL), and Aspergillus flavus (MIC 15?μg/mL), respectively. Compounds 5a and 5b were also found to be active against the tested microorganisms.
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
Kumar, Achutha Dileep,Prabhudeva, Malledevarapura Gurumurthy,Bharath, Srinivasan,Kumara, Karthik,Lokanath, Neratur Krishnappagowda,Kumar, Kariyappa Ajay
, p. 444 - 452 (2018/07/13)
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.
