Rahul D. Kamble

Green approach towards synthesis of substituted pyrazole-1,4-dihydro,9-oxa,1,2,6,8-tetrazacyclopentano[b]naphthalene-5-one derivatives as antimycobacterial agents

In the present communication, a simple and efficient synthesis of some new Pyrano-[2,3-c]-pyrazoles derivatives are described by the one-pot condensation of a mixture of 3-methyl-1-phenyl-1H-pyrazole-5(4H)-one, substituted heterylaldehydes and malononitriles in polyethylene glycol (PEG-400) as green reaction solvent, further reacted with substituted acetophenones in the presence of polyethylene glycol (PEG-400) to form naphthalene analogues. Synthesis of novel substituted naphthalene analogues libraries are currently of high interest. The chemical structures of newly synthesized compounds were confirmed by IR, 1H NMR and Mass spectral analysis. In vitro antimycobacterial activities of newly synthesized compounds were investigated against Mycobacterium smegmatis,Mycobacterium pheli and Mycobacterium tuberculosis species. The result revealed that most of the compounds showed good to moderate Antimycobacterial activity.

Synthesis and in silico investigation of thiazoles bearing pyrazoles derivatives as anti-inflammatory agents

Searching novel, safe and effective anti-inflammatory agents has remained an evolving research enquiry in the mainstream of inflammatory disorders. In the present investigation series of thiazoles bearing pyrazole as a possible pharmacophore were synthesized and assessed for their anti inflammatory activity using in vitro and in vivo methods. In order to decipher the possible anti-inflammatory mechanism of action of the synthesized compounds, cyclooxygenase I and II (COX-I and COX-II) inhibition assays were also carried out. The results obtained clearly focus the significance of compounds 5d, 5h and 5i as selective COX-II inhibitors. Moreover, compound 5h was also identified as a lead molecule for inhibition of the carrageenin induced rat paw edema in animal model studies. Molecular docking results revealed significant interactions of the test compounds with the active site of COX-II, which perhaps can be explored for design and development of novel COX-II selective anti-inflammatory agents.

Bleaching earth clay (pH 12.5): a green catalyst for rapid synthesis of pyranopyrazole derivatives via a tandem three-component reaction

Efficient three-component synthesis of pyranopyrazole derivatives by reacting substituted aromatic aldehydes (1), (4-chlorophenyl)acetonitrile (2) and 3-methyl-1H-pyrazol-5(4H)-one (3) using bleaching earth clay (pH 12.5) as heterogeneous catalyst and PEG-400 as green solvent is reported in the present communication. The reaction time and product yields are excellent. Catalyst and solvent recovery and reusability are very good. This is a simple, green and rapid method for synthesis of pyranopyrazole derivatives.

Green synthesis and in silico investigation of dihydro-2H-benzo[1,3]oxazine derivatives as inhibitors of Mycobacterium tuberculosis

In the midst of increasing multidrug resistance and the growing incidence of infections of Mycobacterium tuberculosis, there is compelling evidence for the synthesis of novel and effective anti-tuberculosis agents. In this report, we have synthesized, characterized, and evaluated benzo[1,3]oxazine derivatives as growth inhibitors of M. tuberculosis. Among the synthesized, dihydro-2H-benzo[1,3]oxazine derivatives, the compounds 5a, 5b, 5d, and 5h showed promising activity against M. tuberculosis when compared with currently used drugs such as Refampicin and Ethambutol. The structure–activity relationship indicates the significance of nitro, chloro, and methoxy group for the manifestation of antimycobacterial activity. Docking studies revealed the binding position of 5a, 5b, and 5h into active cleft of ribosomal A-site indicating the potential target binding molecules against M. tuberculosis.

An efficient synthesis of isoxazoline libraries of thiophene analogs and its antimycobacterial investigation

Synthesis of novel thiophene substituted isoxazoline libraries is currently of high interest. Here, we have reported detailed syntheses of 2,5-dichlorothiophene, 5-chloro-2-(benzylthio)thiophene, and 5-chlorothiophene-2-sulphonamide substituted analogs of isoxazoline from chalcones catalyzed by NaOH in PEG-400 as green solvent. In vitro antimycobacterial and antimicrobial activity of newly synthesized compounds were investigated. Compounds 2j, 2k, and 2l showed excellent activity against Mycobacterium tuberculosis and other Mycobacterium strains tested. Compounds 2a–2c, 2i showed excellent activity against all bacterial and fungal species tested. The isoxazoline scaffold synthesized in the present study may be useful in the development of novel new antimicrobial agents.Graphical abstractAn efficient synthesis of isoxazoline libraries of thiophene analogs and its antimycobacterial investigation.

“Green synthesis” of benzothiazepine library of indeno analogues and their in vitro antimicrobial activity

A novel series of indeno-benzothiazepine derivatives was synthesised via a “green” route. Synthesis of these compounds involves the treatment of dinucleophiles such as 2-aminobenzenethiols with α,β-unsaturated ketones in poly(oxyethylene) (poly(ethylene glycol), PEG-400) catalysed by acetic acid. The synthone α,β-unsaturated ketones were obtained by Claisen-Schmidt condensation of indan-1-one with substituted pyrazole-2-carbaldehydes prompted by bleaching earth (pH 12.5) as catalyst and PEG-400 as “green” reaction solvent. Screening of all the synthesised compounds for antimicrobial activity revealed that most of these compounds exhibited moderate to significant antimicrobial activity.

Antidiabetic and allied biochemical roles of new chromeno-pyrano pyrimidine compounds: synthesis, in vitro and in silico analysis

Diabetes is embracing the human population in logarithmic fashion both in developed as well as developing countries. Aldose reductase is one of the important enzymes of polyol pathway of sugar metabolism in humans. Aldose reductase inhibition has been identified as one of the important target for developing novel antidiabetic agents. In this report, we present an effective synthesis of 7-(substituted phenyl) chromeno-pyrano [2,3-d]pyrimidine-6,8,10-(7H,9H,11H)-trione derivatives and demonstrate their aldose reductase inhibition potential in order to identify novel schemes for finding putative aldose reductase inhibitors. The antioxidant activity of all the synthesized compounds with negligible toxicity demonstrates the biological efficacy of the synthesized compounds. The in silico molecular docking and structural analysis of docked poses conducted in the current investigation sheds light on the structural rationale of the observed aldose reductase inhibition by all the newly synthesized compounds.

Synthesis and molecular docking studies of a new series of bipyrazol-yl-thiazol-ylidene-hydrazinecarbothioamide derivatives as potential antitubercular agents

Various substituted 2-(2-(5-(3/4-substituted phenyl)-4-hydroxy-3′-(3/4-substituted phenyl)-1′-phenyl-1H,1′H-[3,4′-bipyrazol]-1-yl)thiazol-4(5H)ylidene) hydrazinecarbothioamide derivatives have been synthesized in good yields by an efficient method. The synthesized compounds (6a–r) were evaluated for their in vitro antitubercular activity against the Mycobacterium tuberculosis (MTCC 300) strain. Compounds 6o (MIC-3.90 μg mL−1), 6p (MIC-3.90 μg mL−1), and 6q (MIC-7.81 μg mL−1), exhibited significant activity against Mycobacterium tuberculosis. The molecular docking studies revealed an interesting binding profile with very high receptor affinity.

Green method for synthesis of 3-[2-(substituted-phenyl)-2-oxo ethylidene]-1,3-dihydro-indol-2-one and their in vitro antimicrobial activity

The cross-aldol condensation between isatin (I) and substituted acetophenone (IIa–e) in one-pot reaction afforded 3-[2-(substituted-phenyl)-2-oxo-ethylidene]-1,3-dihydro-indol-2-one using polyethylene glycol (PEG-400) as solvent and bleaching earth clay (pH 12.5) as a catalyst at room temperature. The PEG 400, bleaching earth are recyclable green solvent and catalyst, respectively. The formed compounds were confirmed by spectral analysis. These compounds show significant antimicrobial activity.

Bleaching earth clay pH 12.5/PEG-400 catalytic system for synthesis of some novel α, β-unsaturated ketones (chalcones)

We report bleaching earth clay pH 12.5/PEG-400 as an efficient catalytic system for preparation of α,β-unsaturated ketones (chalcones). The method presents one or more advantages over existing methodologies such as shorter reaction time, excellent yield, and low cost. All synthesized products were characterized by spectroscopic and analytical measurements.