Synthesis and antibacterial activity of new 1,2,3-triazolylmethyl-2H-1,4-benzothiazin-3(4H)-one derivatives

Abstract

BackgroundA novel series of 1,2,3-triazole derivatives containing 1,4-benzothiazin-3-one ring (7a–9a, 7b–9b), (10a–12a, 10b–12b) and (13–15) were synthesized by 1,3-dipolar cycloaddition reactions of azides α-d-galactopyranoside azide F, 2,3,4,6-tetra-O-acetyl-(d)-glucopyranosyl azide G and methyl-N-benzoyl-α-azidoglycinate H with compounds 4–6.FindingsInitially, the reactions were conducted under thermal conditions in ethanol. The reaction leads, each time, to the formation of two regioisomers: (Schemes 2, 3) with yields of 17 to 21% for 1,5-disubstituted 1,2,3-triazole-regioisomers (7b–12b) and yields ranging from 61 to 65% for the 1,4-disubstituted regioisomers (7a–12a). In order to report an unequivocal synthesis of the 1,4-regioisomers and confirm the structures of the two regioisomers obtained in thermal conditions (Huisgen reactions), the method click chemistry (Copper-Catalyzed Azide-Alkyne Cycloaddition) has been used.ConclusionsThe newly synthesized compounds using cycloaddition reactions were evaluated in vitro for their antibacterial activities against some Gram positive and Gram negative microbial strains. Among the compounds tested, the compound 8a showed excellent antibacterial activities against PA ATCC and Acin ESBL (MIC = 31.2 μg/ml).

Crystal structure, Hirshfeld surface analysis and interaction energy, DFT and antibacterial activity studies of ethyl 2-[(2Z)-2-(2-chlorobenzylidene)-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-4-yl]acetate

“…They have also been reported as precursors for the syntheses of new compounds (Sebbar et al, 2015a;Vidal et al, 2006) possessing anti-diabetic (Tawada et al, 1990) and anti-corrosion (Ellouz et al, 2016a,b) activities, and as antiproliferative (Zięba et al, 2010) or antihelmintic (Munir- ISSN 2056-9890 ajasekar et al, 2011) agents. The biological activities of some 1,4-benzothiazines are similar to those of phenothiazines, featuring the same structural specificity (Hni et al, 2019a,b;Ellouz et al, 2017aEllouz et al, , 2018Ellouz et al, , 2019Sebbar et al, 2019a,b). In a continuation of our research activities devoted to the development of N-substituted 1,4-benzothiazine derivatives and the evaluation of their potential pharmacological activities (Ellouz et al, 2017a;Sebbar et al, 2017a), we have synthesized a new heterocyclic system containing 1,4-benzothiazine.…”

“…A number of pharmacological tests have revealed 1,4-benzothiazine derivatives to possess a wide spectrum of biological applications, indicating that the 1,4-benzothiazine moiety is a potentially useful template in medicinal chemistry research and therapeutic applications such as in vivo antiproliferative (Zięba et al, 2016), antibacterial (Sebbar et al, 2016b;Ellouz et al, 2019), antimicrobial (Armenise et al, 2012;Sabatini et al, 2008;Vijay & Rahul, 2016), anti-viral (Malagu et al, 1998), anti-oxidant (Zia-ur-Rehman et al, 2009), anti-inflammatory (Trapani et al, 1985;Gowda et al, 2011), antipyretic (Warren & Knaus, 1987) and anti-cancer (Gupta & Gupta, 1991;Gupta et al, 1985) areas. They have also been reported as precursors for the syntheses of new compounds (Sebbar et al, 2015a;Vidal et al, 2006) possessing anti-diabetic (Tawada et al, 1990) and anti-corrosion (Ellouz et al, 2016a,b) activities, and as antiproliferative (Zięba et al, 2010) or antihelmintic (Munir- ISSN 2056-9890 ajasekar et al, 2011) agents.…”

Crystal structure, Hirshfeld surface analysis and interaction energy, DFT and antibacterial activity studies of (Z)-4-hexyl-2-(4-methylbenzylidene)-2H-benzo[b][1,4]thiazin-3(4H)-one

“…In a continuation of our research devoted to the development of substituted 1,4-benzothiazine derivatives (Ellouz et al, 2015(Ellouz et al, , 2019; Sebbar et al, 2015, 2017a; Ellouz et al), we have ISSN 2056-9890 synthesized the title compound, I, by reaction of hexyl chloride with 2-(4-methylbenzylidene)-3,4-dihydro-2H-1,4benzothiazin-3 -one and potassium carbonate in the presence of tetra-n-butylammonium bromide (as catalyst). We report herein the synthesis, the molecular and crystal structures along with the Hirshfeld surface analysis and interaction energy calculation p) energy model] and the density functional theory (DFT) computational calculation carried out at the B3LYP/6-311 G(d,p) level for comparing with the experimentally determined molecular structure in the solid state of the title compound.…”

Crystal structure, Hirshfeld surface analysis and DFT study of (2Z)-2-(4-fluorobenzylidene)-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-1,4-benzothiazin-3-one

“…Recent research has been focused on existing molecules and their modifications in order to reduce their side effects and to explore their other pharmacological and biological effects Sebbar et al, 2016b;Gautam et al, 2012). As a continuation of our research into the development of N-substituted 1,4-benzothiazine derivatives and the evaluation of their potential pharmacological activities, we have studied the condensation reaction of propargyl bromide with (Z)-2-(4-fluorobenzyl- idene)-2H-1,4-benzothiazin-3(4H)-one under phase-transfer catalysis conditions using tetra-n-butylammonium bromide (TBAB) as catalyst and potassium carbonate as base, leading to the title compound namely (2Z)-2-(4-fluorobenzylidene)-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-1,4-benzothiazin-3-one in good yield (Sebbar et al, 2017a, Ellouz et al, 2018, and we report herein its synthesis, the molecular and crystal structures, along with the Hirshfeld surface analysis and density functional theory (DFT) computational calculations carried out at the B3LYP/6-311 G(d,p) level.…”