Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent

Shaikh, Mubarak H.; Subhedar, Dnyaneshwar D.; Arkile, Manisha; Khedkar, Vijay M.; Jadhav, Nandadeep J.; Sarkar, Dhiman; Shingate, Bapurao B.

doi:10.1016/j.bmcl.2015.11.071

Cited by 102 publications

(32 citation statements)

References 58 publications

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“…Recently, regioselectivity of the reaction was improved by Sharpless and Meldal by introducing Cu(I) catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) to afford 1,4-disubstituted 1,2,3-triazole [19,20]. The triazole nucleus is an important pharmacophore appearing extensively in various types of pharmaceutical agents and bioactive molecules, such as anti-HIV [21], antitubercular [22], anti-inflammatory, anticancer [23], antimicrobial [24], anticonvulsant [25], V. S. Dofe et al antimalarial [26], analgesic [27], antiviral [28], antidiabetic [29], antimycobacterial [30], and anticholinesterase [31]. The biological activity of these compounds is enhanced probably due to their high aromatic stabilisation, high dipole moment, and high bonding capacity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, antimicrobial evaluation, and molecular docking studies of novel chromone based 1,2,3-triazoles

et al. 2016

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In Search of novel antimicrobial agents with improved potency, we designed and synthesized a series of 3-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-2-(4-fluorophenyl)-4H-chromen-4-ones 5a-f using click chemistry. The structures of synthesized compounds were found using IR, 1 H NMR, 13 C NMR, and MS. All the synthesized compounds were assayed for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa and antifungal activity against Candida albicans, Candida glabrata, and Candida tropicalis by micro broth dilution method. The antimicrobial data suggested that from the series, compounds 3e, 4e, 5e, and 5f shows pronounced antimicrobial activity against the tested strain with low MIC value. Molecular docking study was used to rationalize binding interaction at the active site and the results showed good binding interaction.Electronic supplementary material The online version of this article (

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Section: Introductionmentioning

confidence: 99%

Synthesis, antimicrobial evaluation, and molecular docking studies of novel chromone based 1,2,3-triazoles

et al. 2016

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“…Compound 44 (Figure ), the most active in all of the compounds, synthesized presented an IC 50 of 1.24 μg/ml. However, it was less active than the control drugs, which showed IC 50 values ranging from 0.0018 to 0.0025 μg/ml (Shaikh et al, ).…”

Section: Five‐membered Ring Compoundsmentioning

confidence: 99%

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Wang

et al. 2020

Drug Development Research

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Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease.To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure-activity relationships, and mechanisms of action. K E Y W O R D Santi-TB drug, antitubercular activities, five-membered ring, MDR-TB, tuberculosis

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“…Recombinant M. tuberculosis DprE1 was overexpressed and purified as described 16 previously (5) to obtain highly concentrated and pure protein with bound flavin adenine 17 dinucleotide (FAD). Enzyme activities in the presence of MCZ, Ty38c and 11326127 were 18 measured as described previously to determine IC 50 (50% inhibitory concentrations) values for 19 both wild-type and C131S mutant DprE1 proteins (14). solutions were pre-incubated at 37°C for 10 min before the intrinsic clearance assessment was 18 initiated by mixing the two solutions (50 µl of each; final compound concentration, 1 µg/ml) at 19 37°C.…”

Section: Inhibition Assays Crystallography and Structural Studies Ofmentioning

confidence: 99%

Structure-based drug design and characterization of sulfonyl-piperazine benzothiazinone inhibitors of DprE1 from Mycobacterium tuberculosis

Piton

Vocat

Lupien

et al. 2018

Preprint

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Macozinone (MCZ) is a tuberculosis (TB) drug candidate that specifically targets the essential flavoenzyme DprE1 thereby blocking synthesis of the cell wall precursor decaprenyl phosphoarabinose (DPA) and provoking lysis of Mycobacterium tuberculosis. As part of the MCZ back-up program we exploited structure-guided drug design to produce a new series of sulfone-containing derivatives, 2-sulphonylpiperazin 8-nitro 6-trifluoromethyl 1,3-benzothiazin-4-one, or sPBTZ. These compounds are less active than MCZ but have a better solubility profile and some derivatives display enhanced stability in microsomal assays. DprE1 was efficiently inhibited by sPBTZ and covalent adducts with the active site cysteine residue (C387) were formed. However, despite the H-bonding potential of the sulfone group no additional bonds were seen in the crystal structure of the sPBTZ-DprE1 complex with compound 11326127 as compared to MCZ. Compound 11626091, the most advanced sPBTZ, displayed good antitubercular activity in the murine model of chronic TB but was less effective than MCZ. Nonetheless, further testing of this MCZ backup compound is warranted as part of combination treatment with other TB drugs.

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Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent

Cited by 102 publications

References 58 publications

Synthesis, antimicrobial evaluation, and molecular docking studies of novel chromone based 1,2,3-triazoles

Synthesis, antimicrobial evaluation, and molecular docking studies of novel chromone based 1,2,3-triazoles

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Structure-based drug design and characterization of sulfonyl-piperazine benzothiazinone inhibitors of DprE1 from Mycobacterium tuberculosis

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