Ajay Kumar Kariyappa

Synthesis of novel coumarin appended bis(formylpyrazole) derivatives: Studies on their antimicrobial and antioxidant activities

A series of novel coumarin pyrazole hybrids of biological interest were synthesized from the hydrazones, carbazones and thiocarbazones via Vilsmeier Haack formylation reaction. These intermediates and formyl pyrazoles were evaluated for antimicrobial and antioxidant activities. Among the series, compounds 6g and 6h showed excellent antimicrobial activity against different bacterial and fungal strains and compounds 7g, 7h were found to be potent antioxidant agents in both DPPH and hydroxyl radical scavenging assays. Further, detailed quantitative structure-activity relationship (QSAR) analysis indicated the molecular parameters that contribute to increased potency of inhibition. The above findings would further encourage our understanding in employing coumarin pyrazole hybrids as potential antibiotic agents for treating infections caused by pathogenic microbes and fungi. Further, it also paves the way for exploration of these compounds as potential therapeutic agents to treat conditions arising because of excessive oxidative damage.

Synthesis of novel 2-pyrazoline analogues with potent anti-inflammatory effect mediated by inhibition of phospholipase A2: Crystallographic, in silico docking and QSAR analysis

Oxidative-stress induces inflammatory diseases. Further, infections caused by drug-resistant microbial strains are on the rise. This necessitates the discovery of novel small-molecules for intervention therapy. A series of 3-(2,3-dichlorophenyl)-1-(aryl)prop-2-en-1-ones are synthesized as intermediates via Claisen-Schmidt reaction approach. Subsequently, these intermediates were transformed into 2-pyrazolines by their reaction with phenylhydrazine hydrochlorides in methanol and few drops of acetic acid under reflux conditions. Synthesized compounds were characterized by spectroscopic, crystallographic and elemental analyses studies and then, were evaluated for their in vitro antimicrobial and anti-inflammatory activities. Amongst the series, 3-(4-chlorophenyl)-5-(2,3-dichlorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (5e), 5-(2,3-dichlorophenyl)-3-(4-fluorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (5c) and 5-(2,3-dichlorophenyl)-3-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (5h) showed significant inhibition of phospholipase A2 with IC50 values of 10.2, 11.1 and 11.9µM, respectively. Protein structure modelling and docking studies indicated that the compounds showed binding to a highly conserved calcium-binding pocket on the enzyme. Further, compounds (5e), 1-(3-chlorophenyl)-5-(2,3-dichlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (5b), and 1-(3-chlorophenyl)-3-(4-chlorophenyl)-5-(2,3-dichlorophenyl)-4,5-dihydro-1H-pyrazole (5f) showed excellent antimicrobial activities against various bacterial and fungal strains. In conclusion, this study is a successful attempt at the synthesis and characterization of chalcone derivatives that can target phospholipase A2, an enzyme that is a prominent player in the physiological inflammatory cascade. Thus, these compounds show promise for development as next-generation nonsteroidal anti-inflammatory drugs.

Design, synthesis of novel furan appended benzothiazepine derivatives and in vitro biological evaluation as potent VRV-PL-8a and H+/K+ ATPase inhibitors

A series of new of furan derivatised [1,4] benzothiazepine analogues were synthesized starting from 1-(furan-2-yl)ethanone. 1-(Furan-2-yl)ethanone was converted into chalcones by its reaction with various aromatic aldehydes, then were reacted with 2-aminobenzenethiol in acidic conditions to obtain the title compounds in good yields. The synthesized new compounds were characterized by 1H NMR, 13C NMR, Mass spectral studies and elemental analyses. All the new compounds were evaluated for their in vitro VRV-PL-8a and H+/K+ ATPase inhibitor properties. Preliminary studies revealed that, some molecules amongst the designed series showed promising VRV-PL-8a and H+/K+ ATPase inhibitor properties. Further, rigid body docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This finding presents a promising series of lead molecules that can serve as prototypes for the treatment of inflammatory related disorder that can mitigate the ulcer inducing side effect shown by other NSAIDs.

An Environmentally Benign Lemon Juice Mediated Synthesis of Novel Furan Conjugated Pyrazole Derivatives and Their Biological Evaluation

A series of furan conjugated pyrazole derivatives were synthesized by an accessible and eco-friendly approach. The method involves the reaction of chalcones and phenylhydrazine hydrochlorides in the presence tetrabutylammonium bromide as phase transfer catalyst (PTC) in freshly extracted lemon juice medium. The reaction afforded a series of triaryl and diaryl substituted pyrazoles in moderate to good yields. Structures of synthesized new pyrazoles were Confirmed by spectral studies and elemental analysis. Preliminary studies showed that, among the synthesized series, compounds 5i and 5j with chloro substitution in one of the aromatic rings and compound 7c exhibited excellent activity against S. aureus, P. aeruginosa, and E. coli species. Compounds 5i and 5j also showed excellent antifungal activity against A. niger, A. flavus, and C. albicans species. Compounds, 5c, 5d, 5i, 5j and 7c exhibited excellent DPPH radical scavenging activity.

Synthesis of coumarin appended 1,3-oxazines as potent antimicrobial and antioxidant agents

A convenient protocol for the synthesis of coumarin appended 1,3-benzoxazine derivatives (4a – 4g) is described. Cyclisation of hydrazones (3a – 3g) using triphosgene in dichloromethane gave the corresponding 1,3-oxazines in a relatively good yield. The proposed structures of newly synthesized compounds were confirmed by spectral methods and elemental analysis. Oxazine derivatives 4a – 4g were evaluated for their in vitro antimicrobial activity against various bacteria and fungi. Compounds 4b and 4d inhibited growth of test microbes thus proving significant antimicrobial activity. In addition, in vitro antioxidant activity of the synthesized compounds was evaluated and compared to that of standards, showing DPPH, NO, and OH radical scavenging properties. Compounds 4b and 4f exhibited higher antioxidant activity than a standard drug.

Crystal structure of 3-(thiophen-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carboxamide

Abstract C15H15N3OS, monoclinic, P21/c (No. 14), a = 10.2852(5) Å, b = 10.1649(5) Å, c = 14.7694(8) Å, β = 107.442(2)°, V = 1473.12(13) Å3, Z = 4, Rgt(F) = 0.0449, wRref(F2) = 0.1275, T = 293(2) K.

An easy procedure for synthesis of 1,3,4-oxadiazines: a potential antimicrobial agents

An efficient and accessible procedure for the synthesis of 1,3,4-oxadiazines was developed. Reaction involves the cyclocondensation of phenylhydrazones catalyzed by a mild base triethylamine to produce 1,3,4-oxadiazines in good yields. The synthesized new compounds were characterized by spectral studies and elemental analyses and were screened to explore in vitro antimicrobial activity against bacteria and fungi species. The compounds displayed good to excellent potency against tested microorganisms, in particular, compound with chloro substitution showed good antimicrobial potential.