Newly synthesized indolizine derivatives — antimicrobial and antimutagenic properties

A series of indolizine derivatives have been synthesized and subjected to antibacterial screening studies. Antibacterial activity of 21 derivatives was investigated against Staphylococcus aureus, Mycobacterium smegmatis, Salmonella typhimurium and Escherichia coli; also, the sensitivity of model yeast Candida parapsilosis and some model filamentous fungi Aspergillus fumigatus, Alternaria alternata, Botrytis cinerea and Microsporum gypseum was tested. Newly synthesized indolizine derivatives have shown selective toxicity to Gram-positive bacteria S. aureus and were also considered to be able to inhibit the acidoresistant rod M. smegmatis. Derivative XXI has shown the highest inhibition effect with the bacteriostatic effect on the cells at the concentration of 25 µg mL−1. The best antifungal activity has been detected in the presence of derivative XIII. Derivative XIII did also affect the morphology of hyphal tips of B. cinerea, which led to enhanced ramification of hyphae. Finally, the antimutagenic activity of derivatives was investigated. Significant antimutagenic activity was registered in case of derivative VIII. The number of induced revertants by mutagen [2-(5-nitrofuryl)acrylic acid] was decreased almost to the level of spontaneous revertants in the lowest applied concentration (50 µg per plate).

[1]  P. Olejníková,et al.  Induction of resistance in Mycobacterium smegmatis. , 2013, Canadian journal of microbiology.

[2]  K. B. Sahu,et al.  Amberlite-IRA-402 (OH) ion exchange resin mediated synthesis of indolizines, pyrrolo [1,2-a] quinolines and isoquinolines: antibacterial and antifungal evaluation of the products. , 2011, European journal of medicinal chemistry.

[3]  Varun Raj Vemula,et al.  INDOLIZINE DERIVATIVES: RECENT ADVANCES AND POTENTIAL PHARMACOLOGICAL ACTIVITIES Review Article , 2011 .

[4]  N. Prónayová,et al.  Synthesis and reductive desulfurization of chiral non-racemic benzothienoindolizines. An efficient approach to a novel bioactive tylophorine alkaloid analogue and 6-phenylindolizidine , 2009 .

[5]  N. Prónayová,et al.  Highly diastereoselective approach to novel phenylindolizidinols via benzothieno analogues of tylophorine based on reductive desulfurization of benzo[b]thiophene , 2009 .

[6]  M. Zahouily,et al.  A Quantitative Structure-Activity Relationship Model , 2008 .

[7]  E. Darwish Facile Synthesis of Heterocycles via 2-Picolinium Bromide and Antimicrobial Activities of the Products , 2008, Molecules.

[8]  R. Pokorný,et al.  Copper complexes with bioactive ligands , 2002, Folia Microbiologica.

[9]  L. Varečka,et al.  Growth and morphogenesis ofBotrytis cinerea. Effects of exogenous calcium ions, calcium channel blockers and cyclosporin A , 1994, Folia Microbiologica.

[10]  R. Pokorný,et al.  Copper complexes with bioactive ligands , 2008, Folia Microbiologica.

[11]  L. Gundersen,et al.  Synthesis of indolizine derivatives with selective antibacterial activity against Mycobacterium tuberculosis. , 2007, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[12]  H. Waldmann,et al.  3-Substituted indolizine-1-carbonitrile derivatives as phosphatase inhibitors. , 2006, Bioorganic & medicinal chemistry letters.

[13]  L. Gundersen,et al.  Indolizine 1-sulfonates as potent inhibitors of 15-lipoxygenase from soybeans. , 2005, Bioorganic & medicinal chemistry.

[14]  Yoshiharu Sato,et al.  Synthesis and properties of highly fluorescent indolizino[3,4,5-ab]isoindoles. , 2004, Journal of the American Chemical Society.

[15]  Anthony Linden,et al.  3-(4-Chlorobenzoyl)-7-(N,N-dimethylamino)-1-phenylindolizine and 3-(2,4-dichlorobenzoyl)-7-(N,N-dimethylamino)-1-phenylindolizine. , 2003, Acta crystallographica. Section C, Crystal structure communications.

[16]  S P Gupta,et al.  A quantitative structure-activity relationship study on a novel class of calcium-entry blockers: 1-[(4-(aminoalkoxy)phenyl)sulphonyl]indolizines. , 2003, European journal of medicinal chemistry.

[17]  L. Gundersen,et al.  Antimycobacterial Activity of 1‐Substituted Indolizines , 2003, Archiv der Pharmazie.

[18]  D. Velmurugan,et al.  3-[2-(2,4-Di­chloro­phenyl)­vinyl]-2-methyl-1-phenyl­sulfonyl-1H-indole , 2003 .

[19]  A. Vlahovici,et al.  A study of the dimethyl 3-benzoyl-5(2′-pyridyl)-indolisine-1,2-dicarboxylate exciplexes with alcohols , 2002 .

[20]  J. M. Miller,et al.  Synthesis and properties of , 2002 .

[21]  Luyi Guo,et al.  Synthesis and mannosidase inhibitory activity of 3-benzyloxymethyl analogs of swainsonine , 2001 .

[22]  A. Ullrich,et al.  Cloning and Characterization of Secretory Tyrosine Phosphatases of Mycobacterium tuberculosis , 2000, Journal of bacteriology.

[23]  M. Ihara,et al.  A concise formal total synthesis of mappicine and nothapodytine B via an intramolecular hetero Diels-Alder reaction. , 2000, The Journal of organic chemistry.

[24]  Eric Deniau,et al.  First synthesis and pharmacological evaluation of benzoindolizidine and benzoquinolizidine analogues of α- and β-peltatin , 2000 .

[25]  U. Resch‐Genger,et al.  Fluorescence and UV/Vis spectroscopic behaviour of novel biindolizines , 2000 .

[26]  K. Wassermann,et al.  Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor. , 2000, Bioorganic & medicinal chemistry letters.

[27]  Mary Jane Ferraro,et al.  Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically : approved standard , 2000 .

[28]  F. Szemes,et al.  Synthesis of Enantiopure (S)-Thieno[f]indolizidines. , 1999 .

[29]  Štefan Marchalín,et al.  Synthesis of Enantiopure (S)-Thieno[f]indolizidines , 1999 .

[30]  A. Bast,et al.  Inhibition of lipid peroxidation mediated by indolizines. , 1998, Bioorganic & medicinal chemistry letters.

[31]  K. Yazawa,et al.  A Synthesis of the Derivatives of 1,2,3,5,10,10a‐Hexahydrobenz(f) indolizine‐6,9‐dione Having Antifungal Activity as a Simple Model of Saframycin A. , 1996 .

[32]  K. Yazawa,et al.  A Synthesis of the Derivative of 1,2,3,5,10,10a-Hexahydrobenz[f]indolizine-6,9-dione Having Antifungal Activity as a Simple Model of SaframycinA , 1996 .

[33]  Stefano Cicchi,et al.  Assignment of the Absolute Configuration of Natural Lentiginosine by Synthesis and Enzymic Assays of Optically Pure (+) and (-)-Enantiomers , 1995 .

[34]  W. Snowden,et al.  Synthesis and Anti-Herpes Activity of a Series of Indolizines , 1995 .

[35]  D. Mastropaolo,et al.  Glucosidase inhibitors: structures of deoxynojirimycin and castanospermine. , 1993, Journal of medicinal chemistry.

[36]  B. Decroix,et al.  Synthesis of indolizine-6,9-diones annelated to a thiophene ring , 1993 .

[37]  P. Polster,et al.  A novel class of calcium-entry blockers: the 1[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines. , 1992, Journal of medicinal chemistry.

[38]  R. Shank,et al.  Antinociceptive action of McN-5195 in rodents: a structurally novel (indolizine) analgesic with a nonopioid mechanism of action. , 1990, The Journal of pharmacology and experimental therapeutics.

[39]  B. Ames,et al.  Revised methods for the Salmonella mutagenicity test. , 1983, Mutation research.