Exploration of Newer Possibilities to the Synthesis of Diazepine and Quinoline Carboxylic Acid Derivatives (original) (raw)
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Indian Journal of Pharmaceutical Education and Research, 2022
Background: Quinolino and diazacino are important heterocyclics moiety, which have been reported to possess various activities such as antiallergenic, antifungal, hypocholesterolemic, antibacterial and antiviral activities. The activities of these compounds were related to inhibition of bacterial dehydrogenase enzyme which is one of the important targets studied for designing of antimicrobial drugs. Further, molecular docking approached is used in the present study for confirming potent molecules. Objectives: Aim of the study is to synthesize a series of quinolino and diazacino condensed analogues and evaluation of their anti-microbial activity. Methods: Quinolino and diazacino condensed analogues of azepino [3, 2-b] carbazole-2-one were synthesized by Friedel-Craft acylation and Pfitzinger reaction. Structures of synthesized compounds were characterized by FTIR and HNMR and were evaluated for antimicrobial activity by in-vitro bacterial dehydrogenase activity agar well diffusion assay. Further, in order to determine the binding affinity, molecular docking of synthesized compounds was also performed using bacterial (3NUH of E. coli) and fungal proteins (1FI4). In addition, bacterial dehydrogenase inhibitory activity of most active compound was performed using MTT assay. Results: Synthesized compounds (3, 4 and 6) caused impressive antibacterial and antifungal activities in-vitro assay when compared to the ciprofloxacin and fluconazole. And molecular docking studies also revealed that the synthesized compounds 3, 4 and 6 exhibits good to excellent affinity towards target microbial proteins. Conclusion: Synthesized compounds (3, 4 and 6) hold substantial antibacterial potential and require further exploration to establish them as therapeutic candidates in clinical management.
Annales Pharmaceutiques Françaises, 2014
Two new rhenium complexes containing pyridine-triazole (pyta) and quinoline-triazole (quinta) ligands with attached glutamine-targeting agents have been characterized and tested for uptake in the HT-29 human colon adenocarcinoma cell line. The glutamine moiety in Re(CO) 3 Br(pyta) (1) and Re(CO) 3 Br(quinta) (2) remains pendant in solution. Both complexes exhibit absorptions in the 300-400-nm range with metal-to-ligand charge transfer (MLCT) character, as predicted by time-dependent density functional theory calculations. Geometrical analysis by theoretical calculations provides information on the cationic complexes 1 ? and 2 ? resulting from aquo for halide ligand exchange under aqueous conditions. The emissive properties of both complexes were studied under aqueous conditions, and the measured quantum yields were 0.46 % for 1 ? and 0.18 % for 2 ?. The large Stokes shifts and oxygen sensitivity of the emission suggest a 3 MLCT process for both complexes. Cell studies in the HT-29 cell line demonstrate that both complexes are nontoxic over a large concentration range (0-1.4 mM). Preliminary uptake studies show that 2 ? , but not 1 ? , displays significant concentration-dependent uptake at 3 and 24 h.
An Expedient One-Pot Synthetic Protocol to the Preparation Of Isoxazolo and Pyrazolo Annulated Analogues of Benzoxazepino Condensed Carbazoles and Azacarbazoles of Medicinal Interest, 2015
A facile one-pot synthetic protocol for the preparation of isoxazolo and pyrazolo annulated analogues of the benzoxazepine condensed carbazoles and azacarbazoles from the corresponding enolic ethers, α, β-unsaturated ketones, oxoketene dithioacetals and dimethylaminomethylene ketones derived from benzoxazepino condensed oxocarbazoles and oxoazacarbazoles has been described. Compounds were realized from the Japp-Klingemann reaction of the diazonium salt of 2-aminodibenzo [b,f] [1,4]oxazepine with 2-hydroxymethylideno cyclohexanone and N-benzyl-3-hydroxymethylidenopiperidin-4-one followed by Fischer indolization of the obtained hydrazone with kent’s acid. The synthesized heterocyclic compounds were characterized by IR, NMR and MS spectral data and in vitro antimicrobial activity of the synthesized compounds was screened against the standard bacterial and fungal strains. Some of these benzoxazepine derivatives have been found to display excellent antimicrobial activity against bacteria and fungi.
Current Organic Synthesis, 2015
Substantial attention has been given in developing novel heterocyclic compounds as these have been found to exhibit varied biological activities. Benzothiazoles belong to one of the special categories of heterocyclic compounds with a wide range of biological activities such as antimicrobial, antitumor, antidiabetic, antitubercular, antimalarial, anticonvulsant, anthelmintic, analgesic, antiinflammatory and many more. These compounds have been serving as leads for researchers who are actively involved in synthesizing and evaluating their biological activities. Such an extensive work has stimulated further development of new benzothiazole derivatives with enhanced biological activities. This review focuses on the various approaches on the synthesis of benzothiazole derivatives viz., conventional, green, combinatorial and microwave-assisted methods. It also highlights various biological activities of the currently synthesized benzothiazoles.
Synthesis of Novel Benzimidazole and Benzothiazole Derivatives
HETEROCYCLES, 2014
were used as potential scaffolds for biologically interesting azoloazine derivatives via their reaction with the diazonium salts of 5-aminopyrazole, 5-amino[1,2,4]triazole and 2-aminobenzimidazole. Coupling of the β-ketosulfones 1 or 2 with diazotized aromatic amines afforded the corresponding arylhydrazone derivatives which have been utilized as versatile building blocks for the synthesis of biologically interesting pyridazine ring systems. readily available from a variety of precursor functionalities and displays a broad range of synthetic versatility. 19,20 These are also important group of intermediates in Michael and Knoevengel reactions. 21 Compounds containing β-ketosulfones moiety have attracted considerable attention of synthetic chemists in the past decade. 22 As part of our ongoing research program directed towards the synthesis of a variety of heterocycles for biological evaluation, 23,34 we report here on the synthesis of several heterocyclic ring systems incorporation benzothiazole and benzimidazole moieties starting from the versatile hitherto unreported 1-(benzothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1) and 1-(1-methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)-1-ethanone (2).
Archiv der Pharmazie, 2013
In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines. Among these compounds, 4-(3-propynylthio)-7-[N-methyl-N-(3-propynyl)sulfamoyl] quinoline shows significant antiprolierative activity against T47D cells with IC 50 values of 0.07 µM. In addition, 2-(3-Propynylthio)-6-[N-methyl-N-(3-propynyl)sulfa-moyl]quinoline and 2-(3-propynylseleno)-6-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline display highly effective atitumor activity against MDA-MB-231 cells, with IC 50 values of 0.09 and 0.50 µM, respectively. Furthermore, most of the tested compounds show a weak cytotoxic effect against the normal HFF-1 cell line. Additionally, in order to suggest a mechanism of action for their activity, all compounds are docked into the binding site of two human cytochrome P450 (CYP) isoenzymes. These data indicate that some of the title compounds display significant cytotoxic activity, possibly targeting the CYPs pathways.
Oriental Pharmacy and Experimental Medicine, 2012
Exceedingly facile protocols based on the reactivity of corresponding oxoketenedithioacetal (4), 2-(dimethylaminomethylene) ketone (5), β-oxoenolether (6) and α, β-unsaturated ketone (7) resulted from 7-ethyl-3,4 dihydroazepino[3,2-b] carbazole-2,5 (1H,7H)-dione (3) on its reaction with base catalyzed condensation of (a) CS 2 + MeI (b) DMF-DMA (c) H-COOEt and (IV) C 6 H 5 CHO respectively, has been explored to provide an easy access of their isoxazole and pyrazole annulated analogues (8-13) of medicinal interest. The key compound 3 from which, the synthesis proceeded was in turn realized on the reaction of commercial 3-amino-9-ethyl carbazole (1) with ethyl succinyl chloride, under the conditions of Friedel-Crafts acylation followed by cyclocondensation of the resulting intermediate 2 with PPA. Isoxazolo and pyrazolo annulated analogues of carbazolo condensed azepinone derivatives (8-13) were screened for their in-vitro antimicrobial potential against various bacterial and fungal species. Besides this pyrazole derivative (8) was also evaluated for its CNS depressant potential in mice using photoactometer. Keywords Friedel-Crafts acylations. 3-amino-9-ethyl carbazole. Ethyl ester of succinyl chloride. Oxoketnedithioacetal. 2-(dimethylaminomethylene) ketone. Dimethyl formamide dimethyl acetal. Oxoenolether. Chalcone. Isoxazole. Pyrazole Literature has been replete with examples showing that heterocycles which incorporate carbazoles (Mulwad and Patel 2005), azepinones (Kunick and Link 1995), isoxazoles