Efficient Synthesis of Spiro[diindenopyridine-indoline]triones Catalyzed by PEG-OSO₃H-H₂O and [NMP]H₂PO₄

<div><p></p><p>One-pot, three-component synthesis of spiro[diindenopyridine-indoline]triones has been reported via the reaction of 1,3-indandione, aromatic amines, and isatins with (PEG-OSO₃H) as an efficient, polymeric acid surfactant–based catalyst in water and also in presence of acidic ionic liquid [NMP]H₂PO₄, which acts both as a medium and catalyst under conventional heating and ultrasonic irradiation. The reactions were complete in short reaction times with excellent yield of products. Surfactant-based PEG-OSO₃H could be recycled and reused several times without any significant loss of activity. The compounds exhibit fluorescence in methanol with large Stokes shift.</p> </div

Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents

Abstract Background Acyl hydrazones are an important class of heterocyclic compounds promising pharmacological characteristics. Malaria is a life-threatening mosquito-borne blood disease caused by a plasmodium parasite. In some places, malaria can be treated and controlled with early diagnosis. However, some countries lack the resources to do this effectively. Results The present work involves the design and synthesis of some novel acyl hydrazone based molecular hybrids of 1,4-dihydropyridine and pyrazole (5a–g). These molecular hybrids were synthesised by condensation of 1,4-dihydropyridin-4-yl-phenoxyacetohydrazides with differently substituted pyrazole carbaldehyde. The final compound (5) showed two conformations (the major, E, s-cis and the minor, E, s-trans) as revealed by NMR spectral data and further supported by the energy calculations (MOPAC2016 using PM7 method). All the synthesised compounds were screened for their in vitro antimalarial activities against chloroquine-sensitive malaria parasite Plasmodium falciparum (3D7) and antimicrobial activity against Gram positive bacteria i.e. Bacillus cereus, Gram negative bacteria i.e. Escherichia coli and antifungal activity against one fungus i.e. Aspergillus niger. All these compounds were found more potent than chloroquine and clotrimazole, the standard drugs. Conclusions In vitro antiplasmodial IC50 value of the most potent compound 5d was found to be 4.40 nM which is even less than all the three reference drugs chloroquine (18.7 nM), pyrimethamine (11 nM) and artimisinin (6 nM). In silico binding study of compound 5d with plasmodial cysteine protease falcipain-2 indicated the inhibition of falcipain-2 as the probable reason for the antimalarial potency of compound 5d. All the compounds had shown good to excellent antimicrobial and antifungal activities

Efficient One Pot Synthesis of Xanthene-Triazole-Quinoline/Phenyl Conjugates and Evaluation of their Antimicrobial Activity

Novel xanthene-triazole-quinoline/phenyl conjugates were synthesized by eco-friendly one pot three-component condensation of 12-aryl-2-hydroxy-tetrahydrobenzo&#091;a&#093;xanthene-11-one, propargyl bromide and 4-azido-7-chloroquinoline/phenyl azide using polyethylene glycol (PEG-400) as a reaction medium with an aim to explore their effect on the invitro growth of microorganisms causing microbial infection. All newly synthesized xanthene-triazole-quinoline/phenyl conjugates were fully characterized and were evaluated for invitro antibacterial and antifungal activity. Antimicrobial activity was evaluated against nine microbial strains. All compounds showed good Gram positive antibacterial and antifungal activity. One of the compounds showed best antibacterial and antifungal activity. Further, binding mode of this compound at the active site of enzyme topoisomerase II DNA gyrase B has also been investigated

CORAL: probing the structural requirements for α-amylase inhibition activity of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one derivatives based on QSAR with correlation intensity index, molecular docking, molecular dynamics, and ADMET studies

The present study aims to examine the structural requirements governing α-amylase inhibitory activity of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one derivatives and their precursors by employing a multifaceted approach combining in vitro and in silico studies. The in vitro assay findings revealed strong inhibitory effect of this class of compounds against α-amylase and compound 20 exhibited maximum percentage inhibition of 88.54 ± 0.69, 84.98 ± 0.40, 77.26 ± 0.75, 67.80 ± 0.54, and 62.93 ± 1.17 at 200, 100, 50, 25, and 12.5 µg mL−1, respectively. Multiple CORAL QSAR models were developed from the randomly distributed eight splits by employing two target functions (TF1, TF2 with WCII = 0.0 and = 0.3, respectively), and the quality of predictions by the produced models was validated with the help of various statistical parameters. The model M-4 (R2Val = 0.8799) and model M-11 (R2Val = 0.9064) were the leading models developed by using TF1 and TF2. We designed five new congeneric inhibitors (D-1 to D-5) by incorporating SMILES features positively correlating with the activity. Molecular docking experiments were carried out to confirm the binding of these new inhibitors with the biological receptor α-amylase (PDB ID: 7TAA). Furthermore, molecular dynamic simulations provided a thorough knowledge of the binding process by shedding insight into the dynamic behavior and stability of the ligand-receptor complex over time. The results of this study highlight the key structural characteristics needed for improved α-amylase inhibitory efficacy and provide a rational basis for the development of more effective inhibitors. Communicated by Ramaswamy H. Sarma</p

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective

Funding Information: Sandhya Chahal would like to thank CCS HAU for financial assistance in the form of a University Research Scholarship. Payal Rani and Kiran would like to thank UGC for financial assistance in the form of a Senior Research Fellowship. Gaurav Joshi would like to thank Department of Biotechnology, New Delhi, India (Grant No. BT/PR47642/CMD/150/24/2023) for work in the area of COX inhibitors development. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.Innate inflammation beyond a threshold is a significant problem involved in cardiovascular diseases, cancer, and many other chronic conditions. Cyclooxygenase (COX) enzymes are key inflammatory markers as they catalyze prostaglandins production and are crucial for inflammation processes. While COX-I is constitutively expressed and is generally involved in “housekeeping” roles, the expression of the COX-II isoform is induced by the stimulation of different inflammatory cytokines and also promotes the further generation of pro-inflammatory cytokines and chemokines, which affect the prognosis of various diseases. Hence, COX-II is considered an important therapeutic target for drug development against inflammation-related illnesses. Several selective COX-II inhibitors with safe gastric safety profiles features that do not cause gastrointestinal complications associated with classic anti-inflammatory drugs have been developed. Nevertheless, there is mounting evidence of cardiovascular side effects from COX-II inhibitors that resulted in the withdrawal of market-approved anti-COX-II drugs. This necessitates the development of COX-II inhibitors that not only exhibit inhibit potency but also are free of side effects. Probing the scaffold diversity of known inhibitors is vital to achieving this goal. A systematic review and discussion on the scaffold diversity of COX inhibitors are still limited. To address this gap, herein we present an overview of chemical structures and inhibitory activity of different scaffolds of known COX-II inhibitors. The insights from this article could be helpful in seeding the development of next-generation COX-II inhibitors.Peer reviewe

MOESM1 of Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents

Additional file 1. Additional tables

Design, synthesis, DFT, docking studies and ADME prediction of some new coumarinyl linked pyrazolylthiazoles: Potential standalone or adjuvant antimicrobial agents

<div><p>The control of antimicrobial resistance (AMR) seems to have come to a dead end. The major consequences of the use and abuse of antibacterial drugs are the development of resistant strains due to genetic mutability of both pathogenic and nonpathogenic microorganisms. We, herein, report the synthesis, characterization and biological activities of coumarin-thiazole-pyrazole (CTP) molecular hybrids with an effort to explore and overcome the increasing antimicrobial resistance. The compounds were characterized by analyzing their IR, Mass, ¹H and¹³C NMR spectral data and elemental analysis. The <i>in vitro</i> antimicrobial activity of the synthesized compounds was investigated against various pathogenic strains; the results obtained were further explained with the help of DFT and molecular orbital calculations. Compound <b>1b</b> and <b>1f</b> displayed good antimicrobial activity and synergistic effects when used with kanamycin and amphotericin B. Furthermore, i<i>n vitro</i> cytotoxicity of compounds <b>1b</b> and <b>1f</b> were studied against HeLa cells (cervical cancer cell) and Hek-293 cells. The results of molecular docking study were used to better rationalize the action and prediction of the binding modes of these compounds.</p></div

Some thiazole, pyrazole, 4-aryldiazenylpyrazole and coumarin containing biological active heterocycles and target compounds.

<p>Some thiazole, pyrazole, 4-aryldiazenylpyrazole and coumarin containing biological active heterocycles and target compounds.</p

Native ligand (grey) overlap with its best docked pose (green) in a re-docking protocol.

<p>Native ligand (grey) overlap with its best docked pose (green) in a re-docking protocol.</p