Design, synthesis, in vitro anticancer and antimicrobial evaluation, SAR analysis, molecular docking and dynamic simulation of new pyrazoles, triazoles and pyridazines based isoxazole

Pyrazole and its derivatives are considered a privileged N-heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.

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Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

“Pyrazolo-Imidazolidinones: Synthesis, Antimicrobial Assessment and Molecular Modelling Studies by Molecular Mechanic and Quantum Mechanic Approach”

In this research, Fe3O4@SiO2@KCC-1@MPTMS@CuII as a new cockscomb flower-like mesoporous nanocomposite was prepared and characterized by various techniques including Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), SEM-based energy-dispersive X-ray (EDX) spectroscopy, inductively coupled plasma-optical emission spectrometry (ICP-OES), thermogravimetric analysis/differential thermal analysis (TGA/DTA), vibrating sample magnetometry (VSM), UV-Vis spectroscopy, and Brunauer–Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH) analyses. The as-prepared Fe3O4@SiO2@KCC-1@MPTMS@CuII mesoporous nanocomposite exhibited satisfactory catalytic activity in the reduction and reductive acetylation of nitroarenes in a water medium and solvent-free one-pot synthesis of some coumarin compounds including 3,3'-(arylmethylene)bis(4-hydroxy-2H-chromen-2-ones) (namely, bis-coumarins) (3a–n) and 2-amino-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitriles (6a–n) along with acceptable turnover numbers (TONs) and turnover frequencies (TOFs). Furthermore, the mentioned CuII-containing mesoporous nanocatalyst was conveniently recovered by a magnet from reaction environments and reused for at least seven cycles without any significant loss in activity, which confirms its good stability.

Diverse and efficient catalytic applications of new cockscomb flower-like Fe3O4@SiO2@KCC-1@MPTMS@CuII mesoporous nanocomposite in the environmentally benign reduction and reductive acetylation of nitroarenes and one-pot synthesis of some coumarin compounds

A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2'-pyrrolidine-3',3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d,h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties. 

https://www.nature.com/articles/s41598-022-17883-9.pdf

Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties

New Coumarin-Pyrazole hybrids: Synthesis, Docking studies and Biological evaluation as potential cholinesterase inhibitors

Sodium dodecyl benzene sulfonate-catalyzed reaction for green synthesis of biologically active benzylpyrazolyl-coumarin derivatives, mechanism studies, theoretical calculations

xiang zheng

Papers

New Coumarin-Pyrazole hybrids: Synthesis, Docking studies and Biological evaluation as potential cholinesterase inhibitors

New Coumarin-Pyrazole hybrids: Synthesis, Docking studies and Biological evaluation as potential cholinesterase inhibitors

Sodium dodecyl benzene sulfonate-catalyzed reaction for green synthesis of biologically active benzylpyrazolyl-coumarin derivatives, mechanism studies, theoretical calculations