Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII8-12

Journal of Enzyme Inhibition and Medicinal Chemistry
Anda-Mihaela OlaruIonel I Mangalagiu

Abstract

A series of 13 compounds having a monoindolizine mono-salt skeleton was designed and synthesised in order to evaluate their antimycobacterial activity. The synthesis is efficient, involving only three steps: two alkylations and one 3 + 2 dipolar cycloaddition. The antimicrobial activity against Mycobacterium tuberculosis H37Rv grown under aerobic conditions was evaluated, eight compounds showing a very good antimycobacterial activity. SAR correlation reveals a certain influence of the R substituent from the para position of benzoyl moiety at position 3 of indolizine. The most active five compounds passed the second stage of anti-TB testing, the assay demonstrating that they are potent against both replicating and non-replicating Mtb, have a bactericidal mechanism of action, are active against drug-resistant Mtb strains, present a moderate to good activity against nontuberculous mycobacteria, a good intracellular activity, and a moderate to high cytotoxicity. For one compound showing a promising anti-TB profile, a complete ADMET study has been performed.

References

Mar 1, 1987·European Journal of Cancer & Clinical Oncology·Y MaeharaK Sugimachi
Jan 1, 1986·Methods in Enzymology·A LundinA Pousette
Mar 15, 1993·Journal of Immunological Methods·S P CrouchJ Fletcher
Feb 13, 2001·Current Opinion in Biotechnology·K Slater
Mar 22, 2001·Advanced Drug Delivery Reviews·P ArturssonK Luthman
Apr 25, 2003·Journal of Pharmaceutical Sciences·Michael J BankerJohn A Williams
May 25, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robert L Walsky, R Scott Obach
Dec 21, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christopher J EndresJashvant D Unadkat
Jan 4, 2006·Proceedings·C C Ogu, J L Maxa
Apr 6, 2006·The AAPS Journal·Praveen V BalimaneSaeho Chong
Jan 11, 2007·Antimicrobial Agents and Chemotherapy·Sang Hyun ChoScott G Franzblau
Aug 5, 2008·Combinatorial Chemistry & High Throughput Screening·Li DiGuy T Carter
Mar 11, 2009·Bioorganic & Medicinal Chemistry·Roxana M Butnariu, Ionel I Mangalagiu
May 15, 2010·Science·Christopher Dye, Brian G Williams
Jun 4, 2010·PloS One·Nuria AndreuSiouxsie Wiles
Sep 4, 2010·European Journal of Medicinal Chemistry·Dorina MantuIonel I Mangalagiu
Dec 2, 2010·Nature Reviews. Drug Discovery·Dennis A SmithEdward H Kerns
May 29, 2012·The Journal of Antimicrobial Chemotherapy·Andrea ZelmerUlrich E Schaible
Jun 26, 2012·Bioorganic & Medicinal Chemistry Letters·Balakrishna DullaManojit Pal
Oct 31, 2012·Expert Review of Anti-infective Therapy·Lorenza Favrot, Donald R Ronning
Mar 13, 2013·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Hitesh R DholariyaKanuprasad D Patel
Nov 26, 2013·European Journal of Medicinal Chemistry·Ramona Danac, Ionel I Mangalagiu
Jan 15, 2015·The Journal of Antimicrobial Chemotherapy·Suresh B LakshminarayanaSrinivasa P S Rao
Apr 18, 2015·Bioorganic & Medicinal Chemistry·Ramona DanacIonel I Mangalagiu
Aug 1, 2016·European Journal of Medicinal Chemistry·Remya RameshD Srinivasa Reddy

❮ Previous
Next ❯

Citations

Oct 4, 2019·Chemical Biology & Drug Design·Jaishree K MaliVikas N Telvekar
Jan 10, 2020·Future Medicinal Chemistry·Vasilichia AntociIonel I Mangalagiu
Jul 21, 2020·Expert Opinion on Therapeutic Patents·Kamal M Dawood, Ashraf A Abbas
Aug 6, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Monica-Cornelia SardaruRamona Danac
Feb 13, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dorina Amariucai-MantuIonel I Mangalagiu
Jul 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dumitrela DiaconuIonel I Mangalagiu
Dec 29, 2020·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Anda-Mihaela CraciunRamona Danac
Jul 3, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Katharigatta N VenugopalaRaghuprasad Mailavaram

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear magnetic resonance
equilibrium dialysis

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.