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This study reports the synthesis and evaluation of a series of new pyridazin-3-ones with furan moieties 5a–j and 6a–f, to test for their antimycobacterial and antifungal activities. The structures of the target compounds were confirmed by elemental analysis and spectroscopic techniques (IR, mass, 1H-and 13C-NMR). Amongst the compounds tested, 5e, 5g, 5i and 6e exhibited highest activity against Mycobacterium tuberculosis, while 5h, 6d and 6f showed moderate in vitro antifungal activities against Candida albicans and Candida parapsilosis.

Dual‐targeting drug design has become a popular approach in investigating and developing potent anticancer agents. In this regard, carbonic anhydrase (CAIX) and vascular endothelial growth factor receptor (VEGFR‐2) are emerging as highly effective targets in the battle against cancer. In the present study, two series of 4‐thiazolidinones/2,4‐thiazolidinediones carrying 2‐methylbenzenesulfonamide derivatives were designed and synthesized as potential dual CAIX/VEGFR‐2 inhibitors. All the target compounds were evaluated against CAIX enzyme compared to dorzolamide and acetazolamide, subsequently the most potent CAIX inhibitors (3a, 3b, 3o, 6d, 6g, and 6i) were selected to evaluate their inhibitory activity against VEGFR‐2 using sorafenib as a reference drug. These compounds were also evaluated against MCF‐7 breast cancer cells and the murine fibroblast 3T3 cell line. According to the results, 3b (CAIX IC50 = 0.035 µM, VEGFR‐2 IC50 = 0.093 µM) and 6i (CAIX IC50 = 0.041 µM, VEGFR‐2 IC50 = 0.048 µM) emerged the most potent compounds against CAIX and VEGFR‐2. Furthermore, docking studies of selected compounds were performed with the CAIX and the tyrosine kinase domain of VEGFR‐2 to comprehend the ligand‐binding interactions. Physicochemical predictions were examined using in silico techniques. In conclusion, these scaffolds present promising leads and furnish promising chemical backbones for the design of potent dual CAIX and VEGFR‐2 inhibitors.b [ABSTRACT FROM AUTHOR]

22 Novel pyridazin‐3‐ones have been designed for anti‐hepatitis B virus (HBV) activity by structural modifications of 3711 which is capsid assembly modulator. Structure of the target compounds were confirmed by elemental analysis and spectroscopic data including X‐ray studies. Among them, the compound having piperazine moiety showed notable inhibitory activity on secretion of HBV DNA and HBeAg which is comparable to that of AT‐130. The preliminary structure‐activity relationships (SARs) of the newly synthesized pyridazin‐3‐one analogues were summarized, which may help researchers to discover more potent anti‐HBV agents bearing pyridazine‐3‐one scaffold. [ABSTRACT FROM AUTHOR]

To develop novel antimycobacterial agents, a new series of thiazolidinone-azole hybrids 4a-b, 5a-b and 6-13 were designed and synthesized. Thiazolidin-4-ones (4a-b and 5a-b) were obtained by the reaction of Schiff bases and hydrazones (2a-b and 3a-b) with mercaptoacetic acid. 5-Benzylidene derivatives (6-13) were gained by treatment of 5a-b with appropriate benzaldehydes according to Knoevenagel condensation. To evaluate their structures ¹H NMR, IR, mass spectrometry and elemental analysis data were used. The target compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv strain using the microplate alamar blue assay method. Among them, 6, 10 and 12 (MIC: 14.27-14.74 µM) were found as most active compounds in the series. It was seen that both phenylamino and benzylidene substitutions on thiazolidin-4-one ring caused an improvement in the antimycobacterial activity. [ABSTRACT FROM AUTHOR]

To find out new agents for treating inflammatory-involved diseases such as Alzheimer's disease, a series of 1,2-diaryl-2-hydroxyiminoethanones containing vicinal diaryl pharmacophore of COX inhibitors were tested by a set of in vitro, in vivo, and computational studies. The in vivo study of compounds indicated their prominent anti-inflammatory ability at the doses of 10 and 20 mg/kg comparable to celecoxib (10 mg/kg). Further in vitro COX-1/ COX-2 evaluations revealed that 4-methoxy derivative 3 had a high selective COX-1 inhibitory activity ( COX-1, IC50 = 0.12 μ m, SI > 833). To evaluate their potential use against Alzheimer's disease, in vitro evaluation of β-amyloid fibril formation using A β(1-40) and A β(1-42) peptides was performed. The evaluation of their antiaggregation ability gave impressive results and comparable to rifampicin and indomethacin. Conformational study of compound 3 and subsequent docking of its restrained analogs on both active sites of COX-1 and COX-2 could provide a proof of its COX-1 selectivity as well as molecular dynamic simulation could elucidate and give more insight into the amyloid disaggregation mechanisms leading to rational design of inhibitors. [ABSTRACT FROM AUTHOR]

In this study, twenty-five new 6-methyl-4,5-dihydropyridazin-3(2 H)-one derivatives having N-acylhydrazone and thiosemicarbazide moieties were synthesized. The target compounds were tested for their antimycobacterial activity in vitro against Mycobacterium tuberculosis HR using the agar dilution method. Among the synthesized compounds, N′-(2,4-dichlorobenzylidene)-2-(3-methyl-6-oxo-5,6-dihydropyridazin-1(4 H)-yl)acetohydrazide 4g was found to be the most active compound with minimum inhibitory concentration of 0.78 μM and was more potent than ethambutol and ciprofloxacin. [ABSTRACT FROM AUTHOR]

In this study, new isoxazolo[4,5-d]pyridazin-4(5H)-one derivatives having an N-acylhydrazone moiety were synthesized. The compounds were tested for their COX inhibitory activities using NS-398 and indomethacine as reference compounds. Although the compounds had an inhibitory profile against both COX-1 and COX-2, most were found to be more selective against COX-2 by a small percentage of inhibition, at the concentration of 50 microM. Docking studies were done to understand the interactions of the tested compounds with the active site of COX-2. It was observed that the compounds fit into, and interacted with, the hydrophobic parts which are common in the active pocket of COX-1 and COX-2 enzymes but could not fit to the area which is specific for COX-2 enzyme., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)