title: Sequential synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole-chromene hybrids and their antimycobacterial evaluation.
abstract: A general method for the synthesis of a library of hitherto unreported amino-1,4-naphthoquinone-appended triazoles was accomplished via a sequential three-component reaction of substituted N-propargylaminonaphthoquinones with variously substituted alkyl bromides/2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in water. Aminonaphthoquinone-appended iminochromene-triazole hybrid heterocycles were also synthesized from the amino-1,4-naphthoquinone-appended-1,2,3-triazolylacetonitriles. All the triazole hybrids were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among the triazoles, 2-(((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione (7d) emerged as the most active one with IC50 = 1.87 μM, being more potent than the anti-TB drugs, cycloserine (6 times), pyrimethamine (20 times) and equipotent as the drug ethambutol (IC50 < 1.56 μM).
authors.affiliation: Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India.
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Devi Bala
authors.affiliation: Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India.
authors.forename: Sivasubramanian
authors.initials: S
authors.lastname: Muthusaravanan
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
authors.forename: Tan Soo
authors.initials: TS
authors.lastname: Choon
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia; New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, Rajasthan 301030, India.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ashraf Ali
authors.affiliation: Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India. Electronic address: subbu.perum@gmail.com.
authors.forename: Subbu
authors.initials: S
authors.lastname: Perumal
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D001578:Benzopyrans; D009285:Naphthoquinones; D014230:Triazoles; C035342:1,4-naphthoquinone
keywords: Click reaction triazole-naphthoquinone hybrid; Mycobacterium tuberculosis; N-Propargylaminonaphthoquinones; Three-component reactions