4H-1,4-Benzothiazine, Dihydro-1,4-benzothiazinones and 2-Amino-5-fluorobenzenethiol Derivatives: Design, Synthesis and in vitro Antimicrobial Screening (original) (raw)
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SPECTRAL EVALUATION AND ANTIMICROBIAL ACTIVITY OF SYNTHESIZED 4H-1,4-BENZOTHIAZINES
Asian Journal of Pharmaceutical and Clinical Research, 2021
Objective: 4H-1,4-Benzothiazines constitute an important class of heterocycles containing 1,4-thiazine ring fused to benzene ring. They are extensively used as tranquilizer, antispasmodic, central nervous system depressant, antiulcer, antibacterial, antifungal, antioxidant, anticancer agents, fungicides, etc. Therefore, these observations prompted us to synthesize substituted 4H-1,4-benzothiazines and investigate their antimicrobial activity against selected bacterial and fungal strains. Methods: In the present research work, 2-Amino-3,5,6-trichlorobenzenethiol condensed with β-diketones/β-ketoesters in the presence of dimethyl sulfoxide followed by oxidative cyclisation leading to the formation of 4H-1,4-benzothiazines. The spectral investigation confirmed the synthesis of these bioactive compounds. All synthesized compounds were screened for their antimicrobial activity (antibacterial and antifungal) using agar well diffusion method. Results: The minimum inhibitory concentration values of synthesized compounds gave excellent results against bacterial as well as fungal strains (Escherichia coli [Gram negative] MTCC 2939, 58–158 μg/mL, Bacillus subtilis [Gram positive] MTCC 441, 41–124 μg/mL, Streptomyces griseus [Gram negative] MTCC 1998, 85–128 μg/mL, Fusarium oxysporum MTCC 1755, 142–151 μg/mL, Aspergillus niger MTCC 281, 59–78 μg/mL, and Rhizopus stolonifer MTCC 2591, 85–118 μg/mL). Conclusion: Synthesized substituted benzothiazines have potential to be used as a new class of antibacterial and antifungal drugs. Further biomedical research is required to make 4H-1,4-benzothiazines related compounds as potential antibacterial and antifungal drugs.
Heterocyclic Communications, 2013
In recent years, synthesis and biological evaluation of novel 4 H-1,4-benzothiazines and their sulfone derivatives have gained momentum due to their medicinal and industrial importance. Our studies focused on the design and synthesis of new antimicrobial agents, and for this purpose a series of novel 4 H-1,4-benzothiazines and their sulfone derivatives were synthesized and their in vitro antimicrobial assessment was carried out against a representative panel of Gram-positive and Gram-negative bacteria strains and selected fungi species. The reported 4 H-1,4-benzothiazines were prepared by condensation followed by oxidative cyclization of substituted 2-aminobenzenethiols with compounds containing active methylene groups. It is believed that the reaction proceeds via intermediary of the enaminoketone system. The sulfone derivatives were synthesized by oxidation of 4 H-1,4-benzothiazines using 30% hydrogen peroxide in glacial acetic acid. Structure determination was done by spectral and elemental investigations.
Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives
Molecules (Basel, Switzerland), 2016
A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1-9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10-18. These were converted to the dibromo compounds 19-27 through reaction with bromine in glacial acetic acid. Compounds 19-27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28-72. Compounds 28-72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-pos...
Synthesis and microbiological activity of some 2H-1,4-Benzothiazin-3-one derivatives
Heterocyclic Communications, 2000
ABSTRACT Synthesis of some novel N-(2-hydroxyl-5-substitutedphenyl)benzacetamides, phenoxyacetamides and thiophenoxyacetamides (5a-k) were described in order to determine their in vitro antimicrobial activity against 3 Gram-positive, 3 Gram-negative bacteria and the fungus Candida albicans comparing with several control drugs. The derivative 5e was found active at a MIC value of 25 micrograms/ml against the whole tested Gram-positive bacteria strains and the Gram-negative microorganism Klebsiella pneumoniae. Moreover, the synthesized compounds 5a-k exhibited significant antibacterial activity against the enterobacter Pseudomonas aureginosae when compared to the control drugs. For the antifungal avtivity against C. albicans, the compound 5k was found more active than the other synthesized derivatives. On the other hand, the antimicrobial activity of some of these acetamide derivatives (5c, 5d, 5e, 5j and 5k) which are the possible metabolites of benzoxazoles, were also compared with their cyclic analogues 6-10. However, most of the MIC values of the benzoxazole derivatives provided better activity than the compared acetamides, while some others of the acetamide derivatives possessed either one fold improved (5d, 5e and 5j) or the same potency (5c, 5d, 5e, 5j and 5k) against the tested microorganisms.
Novel 1,4-benzothiazine derivatives: synthesis, crystal structure, and anti-bacterial properties
Research on Chemical Intermediates, 2016
In order to develop relatively small molecules as pharmacologically active molecules, novel 1,4-benzothiazine derivatives with triazole and oxazolidinone were synthesized. In this study, a series of 1,2,3-triazolylmethyl-1,4-benzothiazine derivatives were developed by exploiting a click chemistry reaction using a CuI-catalyzed Huisgen [3 ? 2] cycloaddition. Starting from 2-(substituted)-3,4dihydro-2H-1,4-benzothiazi-3-one, a number of 1,4-benzothiazine derivatives were also synthesized using different alkylating agents to give a 4-(substituted)-2-(substituted)-3,4-dihydro-2H-1,4-benzothiazi-3-one in good yields. The crystal and molecular structure of compound oxazolidin-2-one in basic benzothiazine was established by single-crystal X-ray diffraction. The newly synthesized products were subjected to in vitro biological evaluation. The result indicated that the compounds show convincing antibacterial activities against different microorganisms. All structures of the synthesized compounds were elucidated on the basis of spectral analyses and chemical reactions.
International Journal of Pharma Research and Health Sciences, 2013
Aim: Benzothiazoles and pyrazoles moieties structurally have better anti inflammatory activity. Therefore various of 8-chloro-7-fluoro-1-[4-methylphenyl] sulphonyl 1,9 dihydro[1,2,4] triazol[3,4-b][1,3] Benzothiazole containing different functional groups have been synthesized by condensing 7-Chloro-6-Fluoro-2-amino-Benzothiazole with hydrazine hydrate in the presence of ethylene glycol and conc. HCl to get 7-chloro-6-fluoro-2-hydrazinyl-1, 3-benzothiazole and then treated with potassium carbonate to get 8-chloro-7-fluoro-1,9a-dihydrol [1,2,4] triazole [3,4-b][1,3] benzothiazole and then treated with p-toulene sulphonamide in the presence of pyridine to get 8-chloro-7-fluoro-1-[4-methylphenyl] sulphonyl-1,9a-dihydro[1,2,4]triazolo[3,4-b][1,3]benzothiazole. To the above product different aromatic amines, as well as various primary and secondary amines in presence of DMF and were treated to get newly targeted compounds by replacing chlorine at 7 th position. The characterization of the compounds were confirmed on the basis of their spectral (IR, 1 H-NMR and MASS) data. Further, they have been screened for their anti-microbial activity. The fungal activity of the compounds was determined by means of the disc-diffusion method. The inhibition zones were measured with a caliper considering the total diameters. The antimicrobial activity of the compounds was determined by means of the disc-diffusion method.
Synthesis and Antimicrobial Activity of some 1, 4-Benzothiazine Derivatives
Journal of Pharmaceutical Research, 2009
Equimolar quantity of 2-aminothiophenol and ethylchloroacetate was condensed and the solid mass obtained was refluxed. The compound obtained was refluxed with 4-aminoacetophenone to produce 3(4'acetylphenylamino) 1,4-benzothiazine. The 3(4'-acetylphenylamino)1,4-benzothiazine was reacted with corresponding aldehyde to give 3[4'-(3"-substituted-2"-propenone-1"-yl) phenylamino]1,4-benzothiazine. The above synthesized compounds and guanidine nitrate were refluxed to afford 3[4'(2"-amino-4"substituted-phenyl)-pyrimidine-4"yl)phenylamino]1,4-benzothiazine. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, FTIR and 1 H-NMR and have been screened for antimicrobial activity.
A series of substituted phenyl[2-(phenylimino)-2H-1,3-thiazin-3(6H)-yl]methanone (3a-t), substituted 4-fluoro-N-{2-(phenylimino)-2H-1,3-thiazin-3(6H)-yl]methyl}aniline (4a-j) were synthesized and evaluated for their in vitro antibacterial activity against three Gram-positive bacteria (S.aureus, S. epidermidis, M. luteus) and three Gram-negative bacteria (E. coli, P. aeruginosa, K. pneumoniae) by paper disc diffusion technique. N-[4,6diphenyl-3,6-dihydro-2H-1,3-thiazin-2-ylidene]aniline reacts with various substituted benzoyl chloride and 4-Flouro aniline to give (3a-t) and (4a-j) respectively. All the synthesized compounds were in good agreement with IR and 1 H NMR spectral data. The minimum inhibitory concentrations (MIC in μg/ml) and zone of inhibitions were determined and compared with standard drug Ciprofloxacin. Against all the bacteria, the minimum inhibitory concentration for the most potent compounds was found to be 3.12μg/ml. Among all the synthesized compounds, 4f showed pronounced antibacterial activity due to the presence of-CF 3 against gram positive bacteria.