title: Synthesis and evaluation of small libraries of triazolylmethoxy chalcones, flavanones and 2-aminopyrimidines as inhibitors of mycobacterial FAS-II and PknG.
abstract: A synthetic strategy to access small libraries of triazolylmethoxy chalcones 4{1-20}, triazolylmethoxy flavanones 5{1-10} and triazolylmethoxy aminopyrimidines 6{1-17} from a common substrate 4-propargyloxy-2-hydroxy acetophenone using a set of different reactions has been developed. The chalcones and flavanones were screened against mycobacterial FAS-II pathway using a recombinant mycobacterial strain, against which the most potent compound showed ∼88% inhibition in bacterial growth and substantially induction of reporter gene activity at 100 μM concentration. The triazolylmethoxy aminopyrimdines were screened against PknG of Mycobaceterium tuberculosis displaying moderate to good activity (23-53% inhibition at 100 μM), comparable to the action of a standard inhibitor.
authors.affiliation: Medicinal & Process Chemistry Division, Central Drug Research Institute, CSIR, PO Box 173, Chattar Manzil, Mahatma Gandhi Marg, Lucknow 226001, India.
authors.forename: Namrata
authors.initials: N
authors.lastname: Anand
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.forename: Anindra
authors.initials: A
authors.lastname: Sharma
authors.forename: Sameer
authors.initials: S
authors.lastname: Tiwari
authors.forename: Vandana
authors.initials: V
authors.lastname: Singh
authors.forename: Diwakar K
authors.initials: DK
authors.lastname: Singh
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Srivastava
authors.forename: B N
authors.initials: BN
authors.lastname: Singh
authors.forename: Rama Pati
authors.initials: RP
authors.lastname: Tripathi
mesh_terms: D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044950:Flavanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047188:Chalcones; D004791:Enzyme Inhibitors; D044950:Flavanones; D011743:Pyrimidines; D054852:Small Molecule Libraries; D014230:Triazoles; C012180:2-aminopyrimidine; D017346:Protein Serine-Threonine Kinases; D054889:Fatty Acid Synthase, Type II