Showing papers on "Pyrazoline published in 2022"

Substrate-Switched Chemodivergent Pyrazole and Pyrazoline Synthesis: [3 + 2] Cycloaddition/Ring-Opening Rearrangement Reaction of Azadienes with Nitrile Imines.

Abstract: By virtue of a fundamentally new reaction model of benzofuran-derived azadienes (BDAs), an unprecedented synthesis of biologically important pyrazoles has been achieved through a tandem [3 + 2] cycloaddition/ring-opening rearrangement reaction of BDAs with nitrile imines. The nature and type of substrates are found to act as a chemical switch to trigger two distinct reaction pathways. A minor modification to the substrates allows the access to spiro-pyrazolines.

A comprehensive review on pyrazoline based heterocyclic hybrids as potent anticancer agents

Abstract: Cancer is one of the leading causes of death globally, around 10 million deaths are reported every year due to cancer. Some clinically approved anticancer drugs play a riveting role in its treatment. Still, due to the severe emergence of drug resistance, side effects, and multidrug-resistant cancers due to mutations, it creates a significant demand for novel, potent, and safe candidates as an anticancer agent with diverse mechanisms of action. In medicinal chemistry, several heterocyclic derivatives and hybrids are studied and reported as potent anticancer agents; Pyrazoline is one of the versatile and ubiquitous scaffolds for developing novel anticancer agents. Many pyrazoline scaffolds bearing drugs are used clinically for the treatment of cancer. Few are in the late phase of the clinical trial for treating various cancers, for example, Indibulin, a novel microtubule inhibitor and AT9283. The hybridization strategy of a pyrazoline scaffold with various heterocyclic rings is very promising to minimize the side effects and drug resistance. In light of this pyrazoline containing hybrids monopolize an important place in developing potent, safe and novel anticancer agents. The presented review outlined recent advances studied and reported towards developing pyrazoline-containing hybrids as potent anticancer agents. The review covers synthetic strategy, structure-activity relationship and anticancer activities of pyrazoline hybrid derivatives. The sole purpose is to shed light on the design and development of pyrazoline hybrids compounds with high efficacy and reduced toxicity.

Design and Synthesis of Carbothioamide/Carboxamide-Based Pyrazoline Analogs as Potential Anticancer Agents: Apoptosis, Molecular Docking, ADME Assay, and DNA Binding Studies

Abstract: To discover anticancer drugs with novel structures and expand our research scope, pyrazoline derivatives (3a–3l) were designed and synthesized through cyclization of chalcones with thiosemicarbazide/semicarbazide in CH3COOH as a solvent. All newly synthesized pyrazoline derivatives were fully characterized using several spectroscopic experiments such as 1H, 13C NMR, FT-IR spectroscopy, and mass analysis. By HPLC, the purity of all analogs was found above 95% and both lead compounds (3a and 3h) were also validated by HRMS. Anticancer activity of synthesized pyrazoline derivatives (3a–3l) was investigated by the MTT assay against the human lung cancer cell (A549), human cervical cancer cell (HeLa), and human primary normal lung cells (HFL-1). Staurosporine (STS) was used as a standard drug. The anticancer results showed that two potent analogs 3a and 3h exhibit excellent activity against A549 (IC50 = 13.49 ± 0.17 and 22.54 ± 0.25 μM) and HeLa cells (IC50 = 17.52 ± 0.09 and 24.14 ± 0.86 μM) and low toxicity against the HFL-1 (IC50 = 114.50 ± 0.01 and 173.20 ± 10 μM). The flow cytometry was further used to confirm the anticancer activity of potent derivatives against the A549 cancer cell line. DNA binding interaction of anticancer agents 3a and 3h with Ct-DNA has been carried out by absorption, fluorescence, EtBr (dye displacement assay), circular dichroism, cyclic voltammetry and time-resolved fluorescence, which showed noncovalent binding mode of interaction. Anticancer activity of both lead compounds (3a and 3h) may be attributed to DNA binding. The evaluation of the antioxidant potential of pyrazoline analogs 3a and 3h by 2,2-diphenyl-1-picrylhydrazyl free radical showed promising antioxidant activity with IC50 values of 0.132 ± 0.012 and 0.215 ± 0.025 μg/mL, respectively. In silico molecular docking of pyrazoline derivatives was also performed using autodock vina software against the DNA hexamer with PDB ID: 1Z3F and ADMET properties to explore their best hits.

One-pot synthesis, molecular docking, ADMET, and DFT studies of novel pyrazolines as promising SARS-CoV-2 main protease inhibitors

Abstract: Pyrazoline and its derivatives have numerous prominent pharmacological effects. Focusing on its anti-viral property, we have designed and synthesized three novel pyrazoline derivatives (A1–A3) through one-pot three components and characterized them using different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and UV). These compounds were evaluated against SARS-CoV-2 main protease utilizing in-silico molecular docking studies. The docking results displayed good inhibitory activity of the synthesized compounds. Among them, compound A2 was the most active against targeted protein. The drug-likeness and ADMET properties were predicted to have varied profiles but could still be developed, especially A2. DFT/TD-DFT calculations through B3LYP/6-311G++ level of theory were applied to provide comparable theoretical data along with MEP map and electronic energy gap of HOMO → LUMO.

Bio‐synthesis of ZrO 2 for ZrO 2 @Ag‐S‐CH 2 COOH as the retrievable catalyst for the one‐pot green synthesis of pyrazoline derivatives and their anticancer evaluation

Abstract: In the present work, Ficus benghalensis (F.B.) leaf extract was used for the synthesis of ZrO2 nanoparticles. Further, ZrO2@Ag-S-CH2-COOH was synthesized using biosynthesized ZrO2 and its catalytic potential was examined in the synthesis of pyrazoline from reaction of chalcone and hydrazine hydrate at room temperature. The structural conformation of ZrO2@Ag-S-CH2-COOH has been done using FT-IR, SEM, EDX, XRD, TGA-TDA, XPS, DLS techniques high turnover number (TON) and high turnover frequency (TOF), study. The ZrO2@Ag-S-CH2-COOH demonstrated outstanding catalytic activity for the synthesis of pyrazolines. The structures of the pyrazoline derivatives were confirmed by FT-IR, 1H and 13C NMR and mass spectrometry techniques. Synthesized pyrazoline were tested for anti-cancer activity against human lung cancer cell line A-549 study and confirmed by molecular docking investigations.

Molecular Engineering of Fluorescent Bichromophore 1,3,5-Triaryl-Δ2-Pyrazoline and 4-Amino-1,8-Naphthalimide Molecular Logic Gates

Abstract: Three hybrid 1,3,5-triaryl-Δ2-pyrazoline and 4-amino-1,8-naphthalimide molecular logic gates, differentiated by phenyl, para-N,N-dimethylaniline and ferrocene substituents, were designed and synthesised according to fluorophore-receptor, receptor1-spacer-fluorophore-receptor2 and electron-donor-spacer-fluorophore-receptor format. The electron-rich para-N,N-dimethylaniline and...

Synthesis, Anticancer and Antitubercular Properties of New Chalcones and Their Nitrogen-Containing Five-Membered Heterocyclic Hybrids Bearing Sulfonamide Moiety

Abstract: A new series of sulfonamides, 8a-b, 10, 12, and 14a-b, were synthesized by N-sulfonation reaction with sulfonyl chlorides 6a-b. Five new series of chalcone-sulfonamide hybrids (16-20)a-f were prepared via Claisen–Schmidt condensation of the newly obtained sulfonamides with aromatic aldehydes 15a-f in basic medium. Chalcones substituted with chlorine at position 4 of each series were used as precursors for the generation of their five-membered heterocyclic pyrazoline (22-23)a-d, (24-25)a-b and carbothioamide 27a-f derivatives. The synthesized compounds were evaluated for their anticancer and antituberculosis activities. To determine their anticancer activity, compounds were screened against sixty human cancer cell lines at a single dose (10 μM). Compounds 17a-c were highly active against LOX IMVI (melanoma), with IC50 values of 0.34, 0.73 and 0.54 μM, respectively. Chalcone 18e showed remarkable results against the entire panel of leukemia cell lines with IC50 values between 0.99–2.52 μM. Moreover, compounds 20e and 20f displayed growth inhibition of Mycobacterium tuberculosis H37Rv at concentrations below 10 μM. Although they showed low selectivity in cytotoxicity tests against the Vero cell line, further optimization could advance the potential biological activity of the selected compounds.

Synthesis and Biological Importance of Pyrazole, Pyrazoline, and Indazole as Antibacterial, Antifungal, Antitubercular, Anticancer, and Anti-inflammatory Agents

Abstract: N-heterocycles have always gained greater attention among the scientific community. Indole, indazole, pyrrole, pyrazole, pyrazoline, pyridine, quinoline, and many more such types of heterocycles have gained an utmost attention towards medicinal chemists for their various biological activities. They are effective as anticancer, antimicrobial, anti-inflammatory, antitubercular agents, etc. Looking at the effectiveness and importance of these N-heterocycles, many researchers have synthesized different molecular hybrids containing one or more heterocyclic motifs in one molecule which resulted from interesting results regarding biological activities. This chapter describes some N-heterocyclic hybrid entities, their synthetic pathways with their respective biological activities.

On the Question of the Formation of Nitro-Functionalized 2,4-Pyrazole Analogs on the Basis of Nitrylimine Molecular Systems and 3,3,3-Trichloro-1-Nitroprop-1-Ene

Abstract: Experimental and theoretical studies on the reaction between (E)-3,3,3-trichloro-1-nitroprop-1-ene and N-(4-bromophenyl)-C-arylnitrylimine were performed. It was found that the title process unexpectedly led to 1-(4-bromophenyl)-3-phenyl-5-nitropyrazole instead of the expected Δ2-pyrazoline molecular system. This was the result of a unique CHCl3 elimination process. The observed mechanism of transformation was explained in the framework of the molecular electron density theory (MEDT). The theoretical results showed that both of the possible channels of [3 + 2] cycloaddition were favorable from a kinetic point of view, due to which the creation of 1-(4-bromophenyl)-3-aryl-4-tricholomethyl-5-nitro-Δ2-pyrazoline was more probable. On the other hand, according to the experimental data, the presented reactions occurred with full regioselectivity.

An experimental and computational study of new spiro-barbituric acid pyrazoline scaffolds: restricted rotation vs. annular tautomerism

Abstract: A regioselective [3+2] cycloaddition (32CA) reaction to synthesize unsymmetric spiro-barbituric pyrazolines containing a chromone or phenolic pyrazole moiety was achieved, providing good to excellent yields.

Synthesis and Characterization of Novel 2-(1,2,3-Triazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazoles and 2-(4,5-Dihydro-1H-pyrazol-1-yl)-4-(1H-1,2,3-triazol-4-yl)thiazoles

Abstract: Reactions of 1-(5-methyl)-1H-1,2,3-triazol-4-yl)ethan-1-ones and benzaldehydes in ethanol under basic conditions gave the corresponding chalcones. Reactions of the chalcones combined with thiosemicarbazide in dry ethanol containing sodium hydroxide afforded the corresponding pyrazolin-N-thioamides. Reactions of the synthesized pyrazolin-N-thioamides and several ketones (namely, ethyl 2-chloro-3-oxobutanoate, 2-bromoacetylbenzofuran, and hydrazonoyl chloride) gave the corresponding novel 2-(1,2,3-triazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazoles in high yields (77–90%). Additionally, 2-(4,5-dihydro-1H-pyrazol-1-yl)-4-(1H-1,2,3-triazol-4-yl)thiazoles were obtained in high yields (84–87%) from reactions with N-pyrazoline-thioamides and 4-bromoacetyl-1,2,3-triazoles under basic conditions. The structures of six of the newly synthesized heterocycles were confirmed by X-ray crystallography.

Fluorescence “Turn-off” Sensing of Iron (III) Ions Utilizing Pyrazoline Based Sensor: Experimental and Computational Study

Abstract: A simple pyrazoline-based ‘‘turn off’’ fluorescent sensor 5-(4-methoxyphenyl)-3-(5-methylfuran-2-yl)-1-phenyl-4,5-dihydro-1H-pyrazole (PFM) was synthesized and well characterized by different techniques such as FT-IR, 1H-NMR, 13C-NMR, and mass spectrometry. The synthesized sensor PFM was utilized for the detection of Fe3+ ions. Fluorescence emission selectively quenched by Fe3+ ions compared to other metal ions (Mn2+, Al3+, Fe2+, Hg2+, Cu2+, Co2+, Ni2+, Cd2+, Pb2+, and Zn2+) via paramagnetic fluorescence quenching and showed good anti-interference ability over the existence of other tested metals. Under optimum conditions, the fluorescence intensity of sensor quenched by Fe3+ in the range of 0 to 3 μM with detection limit of 0.12 μM. Binding of Fe3+ ions to PFM solution were studied by fluorescent titration, revealed formation of 1:1 PFM-Fe metal complex and binding constant of complex was found to be of 1.3 × 105 M−1. Further, the fluorescent sensor has been potentially used for the detection of Fe3+ in environmental samples (river water, tap water, and sewage waste water) with satisfactory recovery values of 99–101%.