TY - JOUR

T1 - New nitrofurans amenable by isocyanide multicomponent chemistry are active against multidrug-resistant and poly-resistant Mycobacterium tuberculosis

AU - Krasavin, Mikhail

AU - Parchinsky, Vladislav

AU - Kantin, Grigory

AU - Manicheva, Olga

AU - Dogonadze, Marine

AU - Vinogradova, Tatiana

AU - Karge, Bianka

AU - Brönstrup, Mark

PY - 2017/1/1

Y1 - 2017/1/1

N2 - A set of structurally diverse N-amino δ-lactams decorated with a 5-nitro-2-furyl moiety was synthesized using isocyanide-based multicomponent chemistry and evaluated for antibacterial activity. Three compounds displayed a selective and potent (MIC 22-33 μM) inhibition of M. tuberculosis H37Rv strain growth, while other Gram-positive (MRSA and E. faecium) or Gram-negative (E. coli, P. aeruginosa, A. baumannii, K. pneumoniae) pathogens were not affected. The compounds also displayed moderate-low cytotoxicity, as demonstrated in cell line viability assays. Several multidrug- and poly-resistant patient-derived M. tuberculosis strains were found to be susceptible to treatment with these compounds. The three most potent compounds share a significant structural similarity which provides a basis for further scaffold-hopping analog design.

AB - A set of structurally diverse N-amino δ-lactams decorated with a 5-nitro-2-furyl moiety was synthesized using isocyanide-based multicomponent chemistry and evaluated for antibacterial activity. Three compounds displayed a selective and potent (MIC 22-33 μM) inhibition of M. tuberculosis H37Rv strain growth, while other Gram-positive (MRSA and E. faecium) or Gram-negative (E. coli, P. aeruginosa, A. baumannii, K. pneumoniae) pathogens were not affected. The compounds also displayed moderate-low cytotoxicity, as demonstrated in cell line viability assays. Several multidrug- and poly-resistant patient-derived M. tuberculosis strains were found to be susceptible to treatment with these compounds. The three most potent compounds share a significant structural similarity which provides a basis for further scaffold-hopping analog design.

KW - Antitubercular

KW - Drug resistance

KW - Multicomponent chemistry

KW - N-amino lactams

KW - Nitrofurans

KW - Patient-derived strains

UR - http://www.scopus.com/inward/record.url?scp=85012890575&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2017.02.003

DO - 10.1016/j.bmc.2017.02.003

M3 - Article

C2 - 28214232

AN - SCOPUS:85012890575

VL - 25

SP - 1867

EP - 1874

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 6

ER -