5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines as dual inhibitors of Mycobacterium tuberculosis and influenza virus: Synthesis and evaluation.

Autor: Marvadi SK; Fluro and Agrochemicals Division (Organic Chemistry Division-II), CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India., Krishna VS; Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India., Sinegubova EO; Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russian Federation., Volobueva AS; Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russian Federation., Esaulkova YL; Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russian Federation., Muryleva AA; Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russian Federation., Tentler DG; Institute of Cytology, Russian Academy of Sciences, 4, Tikhorezky Av., 194064, Russian Federation., Sriram D; Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India., Zarubaev VV; Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russian Federation., Kantevari S; Fluro and Agrochemicals Division (Organic Chemistry Division-II), CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India. Electronic address: ksrinivas@iict.res.in.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Sep 15; Vol. 29 (18), pp. 2664-2669. Date of Electronic Publication: 2019 Jul 24.
DOI: 10.1016/j.bmcl.2019.07.040
Abstrakt: This study describes synthesis and evaluation of novel 5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines 7a-o as dual inhibitors of Mycobacterium tuberculosis and influenza virus. Huisgen's [3+2] dipolar cycloaddition of 6-(azidomethyl)-5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline 5 with various alkynes 6a-o using sodium ascorbate and copper sulphate gave new dihydroquinoline-1,2,3-triazoles 7a-o in good to excellent yields. The new compounds were evaluated for in vitro antimycobacterial against M. tuberculosis H37Rv (Mtb) and antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1). Among the fifteen new analogs, compounds 7a (MIC: 3.12 µg/mL), 7j and 7k (MIC: 6.25 µg/mL) were identified as potent antitubercular agents. The virus-inhibiting activity of all the fifteen compounds was found to be moderate, and among them the compound 7l, bearing thiophene moiety appeared the most active with good selectivity index (IC 50  = 19.5 µg/mL; SI = 15). The results presented here will help developing newer dual inhibitors of tuberculosis and influenza virus.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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