Piyush N. Kalaria

Catalytic regioselective synthesis of pyrazole based pyrido[2,3-d]pyrimidine-diones and their biological evaluation

A new type of biopolymer-based heterogeneous catalyst, cellulose supported acidic ionic liquid (Cell-IL), which was developed earlier in our lab, has been found to be very effective for the regioselective synthesis of pyrazole based pyrido[2,3-d]pyrimidine-diones. Its regioselectivity was confirmed by (1)H NMR spectroscopy. All the newly synthesized compounds were characterized by LC-MS, (1)H NMR, (13)C NMR, IR spectroscopy and elemental analysis. The newly synthesized compounds were evaluated for their in vitro antimalarial activity against Plasmodium falciparum, in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and also for their antibacterial activity against a panel of pathogenic strains of bacteria and fungi. Some of them exhibited excellent activity when compared with first line drugs.

Synthesis, characterization and biological screening of novel 5-imidazopyrazole incorporated fused pyran motifs under microwave irradiation

A novel combinatorial library of fused pyran derivatives has been designed and synthesized under microwave irradiation by one-pot three-component cyclocondensation reaction of 5-(1H-imidazol-1-yl)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde with two active methylene compounds and enolizable ketones/phenols in the presence of piperidine as a basic catalyst. All the newly synthesized compounds have been characterized by elemental analysis and various spectroscopic methods. All the final motifs have been screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, preliminary in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv and also for their antimalarial activity against Plasmodium falciparum.

Synthesis, identification and in vitro biological evaluation of some novel 5-imidazopyrazole incorporated pyrazoline and isoxazoline derivatives

In the present study, novel combinatorial libraries of substituted pyrazolines 6a–l and isoxazolines 7a–l have been synthesized via the reactions of chalcones with the hydrazine hydrate and hydroxylamine hydrochloride in ethanol. The title compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains, in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv, in vitro antimalarial activity against Plasmodium falciparum and in vitro antioxidant activity by the ferric-reducing antioxidant power method. Compounds 6k, 6l, 7h and 7k exhibited excellent antibacterial activity and a few of them exhibited moderate antituberculosis activity compared with the first line drugs. Half of the compounds exhibited terrific antimalarial activity and the majority of compounds showed highest antioxidant potency.

Acidic ionic liquid immobilized on cellulose: an efficient and recyclable heterogeneous catalyst for the solvent-free synthesis of hydroxylated trisubstituted pyridines

The synthesis of a novel cellulose supported acidic ionic liquid (Cell-IL) for the solvent-free synthesis of hydroxylated trisubstituted pyridines is reported. Cell-IL was prepared by immobilization of an acidic ionic liquid [1-butyl-3-(3-trimethoxypropyl)-1H-imidazol-3-ium hydrogen sulfate] on cellulose. The viability of this concept has been confirmed by FT-IR, TGA-DTG, 1H NMR and elemental analysis. The Cell-IL showed good thermal stability and exhibited a high catalytic activity in the synthesis of a series of hydroxylated trisubstituted pyridines. It was recovered and reused for the model reaction three times without an appreciable change in its activity.

Green synthesis and pharmacological screening of polyhydroquinoline derivatives bearing a fluorinated 5-aryloxypyrazole nucleus

A novel series of polyhydroquinoline scaffolds 8a–p has been designed and synthesized under ultrasonic irradiation by a one-pot three-component cyclocondensation reaction of 3-methyl-5-substituted aryloxy-1-phenyl-1H-pyrazole-4-carbaldehydes 3a–d with malononitrile 7 and various enhydrazinoketones 6a–e in the presence of piperidine as basic catalyst. All the synthesized compounds have been characterized by various spectroscopic techniques and elemental analysis. All the synthesized compounds were evaluated for their in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and also for their in vitro antimalarial activity against Plasmodium falciparum. Compounds 8c, 8i, 8j, 8l and 8m exhibited excellent antimalarial potency. The cytotoxicity of the synthesized compounds was tested using a bioassay of S. pombe cells at the cellular level. Compounds 8i, 8j, 8k and 8l were found to have maximum toxicity, while compounds 8e, 8m, 8c were found to be less cytotoxic. Some of them displayed luminous antibacterial activity and reasonable antituberculosis activity as compared with the first line drugs.

L-Proline promoted green and regioselective synthesis of a novel pyrazole based trifluoromethylated fused thiazolopyran scaffold and its biological evaluation

A novel approach for the synthesis of a pyrazole based trifluoromethyl substituted fused thiazolopyran scaffold has been claimed by a one-pot four-component tandem type reaction. Pyrazolyl aldehydes 4a–e, substituted carbothioamide 8a–c, α-bromoethylacetate 9 and malononitrile 10 in the presence of L-proline as the catalyst yielded the targeted products in high yields over a short reaction time. All the compounds were screened for their preliminary in vitro antimicrobial activity against a panel of pathogenic strains and in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. All of the compounds were found to be effective against Gram positive bacteria B. subtilis and C. tetani. Some of the compounds exhibited excellent antifungal activity against C. albicans. A few of them also exhibited moderate antituberculosis activity as compared to the first line drugs.

Design, synthesis and molecular docking of novel bipyrazolyl thiazolone scaffold as a new class of antibacterial agents

A new series of bipyrazolyl thiazolone hybrids were designed based on molecular hybridization technique. All the synthesized compounds were characterized by elemental analysis and various spectroscopic methods. They were tested for their in vitro antibacterial activity against two Gram-positive and two Gram-negative bacteria as well as E. coli FabH using Kanamycin B and Penicillin G as the standard drugs. Of the compounds studied, compound 10c (IC50 = 2.1 μM) showed the most effective E. coli FabH inhibitory activity as compared to other members of the series. The molecular docking study indicated that compound 10c was found nicely bound into the active site of E. coli FabH with hydrogen bonds, π–π and π–cation interactions having minimum binding energy ΔGb = −52.27 kcal mol−1.

A review on diverse heterocyclic compounds as the privileged scaffolds in antimalarial drug discovery

The upward extend of malaria collectively with the emergence of resistance against predictable drugs has put enormous pressure on public health systems to introduce new malaria treatments. Heterocycles play an important role in the design and discovery of new malaria active compounds. Heterocyclic compounds have attracted significant attention for malaria treatment because of simplicity of parallelization and the examining power with regard to chemical space. Introduction of a variety of heterocyclic compounds have enabled to maintain the high levels of antimalarial potency observed for other more lipophilic analogues whilst improving the solubility and the oral bioavailability in pre-clinical species. In this review, we present an overview of recent literature to provide imminent into the applications of different heterocyclic scaffolds in fighting against malaria.