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Biotransformation of bromhexine by Cunninghamella elegans, C. echinulata and C. blakesleeana.
Braz J Microbiol. 2017 Apr - Jun; 48(2):259-267.BJ

Abstract

Fungi is a well-known model used to study drug metabolism and its production in in vitro condition. We aim to screen the most efficient strain of Cunninghamella sp. among C. elegans, C. echinulata and C. blakesleeana for bromhexine metabolites production. We characterized the metabolites produced using various analytical tools and compared them with mammalian metabolites in Rat liver microsomes (RLM). The metabolites were collected by two-stage fermentation of bromhexine with different strains of Cunninghamella sp. followed by extraction. Analysis was done by thin layer chromatography, high performance thin layer chromatography, Fourier transform infrared spectroscopy, high performance liquid chromatography and Liquid chromatography-mass spectrometry. The role of Cytochrome P3A4 (CYP3A4) enzymes in bromhexine metabolism was studied. Fungal incubates were spiked with reference standard - clarithromycin to confirm the role of CYP3A4 enzyme in bromhexine metabolism. Three metabolites appeared at 4.7, 5.5 and 6.4min retention time in HPLC. Metabolites produced by C. elegans and RLM were concluded to be similar based on their retention time, peak area and peak response of 30.05%, 21.06%, 1.34%, and 47.66% of three metabolites and bromhexine in HPLC. The role of CYP3A4 enzyme in metabolism of bromhexine and the presence of these enzymes in Cunninghamella species was confirmed due to absence of peaks at 4.7, 5.4 and 6.7min when RLM were incubated with a CYP3A4 enzyme inhibitor - clarithromycin.

Authors+Show Affiliations

Narsee Monjee Institute of Management Studies, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, Vile Parle (W), Mumbai, Maharashtra, India.Narsee Monjee Institute of Management Studies, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, Vile Parle (W), Mumbai, Maharashtra, India. Electronic address: maushmiskumar@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27988088

Citation

Dube, Aman K., and Maushmi S. Kumar. "Biotransformation of Bromhexine By Cunninghamella Elegans, C. Echinulata and C. Blakesleeana." Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology], vol. 48, no. 2, 2017, pp. 259-267.
Dube AK, Kumar MS. Biotransformation of bromhexine by Cunninghamella elegans, C. echinulata and C. blakesleeana. Braz J Microbiol. 2017;48(2):259-267.
Dube, A. K., & Kumar, M. S. (2017). Biotransformation of bromhexine by Cunninghamella elegans, C. echinulata and C. blakesleeana. Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology], 48(2), 259-267. https://doi.org/10.1016/j.bjm.2016.11.003
Dube AK, Kumar MS. Biotransformation of Bromhexine By Cunninghamella Elegans, C. Echinulata and C. Blakesleeana. Braz J Microbiol. 2017 Apr - Jun;48(2):259-267. PubMed PMID: 27988088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biotransformation of bromhexine by Cunninghamella elegans, C. echinulata and C. blakesleeana. AU - Dube,Aman K, AU - Kumar,Maushmi S, Y1 - 2016/12/05/ PY - 2015/07/03/received PY - 2016/07/01/accepted PY - 2016/12/19/pubmed PY - 2017/4/15/medline PY - 2016/12/19/entrez KW - Bromhexine KW - CYP3A4 KW - Cunninghamella sp. KW - Inhibitor KW - Metabolism KW - RLM SP - 259 EP - 267 JF - Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] JO - Braz. J. Microbiol. VL - 48 IS - 2 N2 - Fungi is a well-known model used to study drug metabolism and its production in in vitro condition. We aim to screen the most efficient strain of Cunninghamella sp. among C. elegans, C. echinulata and C. blakesleeana for bromhexine metabolites production. We characterized the metabolites produced using various analytical tools and compared them with mammalian metabolites in Rat liver microsomes (RLM). The metabolites were collected by two-stage fermentation of bromhexine with different strains of Cunninghamella sp. followed by extraction. Analysis was done by thin layer chromatography, high performance thin layer chromatography, Fourier transform infrared spectroscopy, high performance liquid chromatography and Liquid chromatography-mass spectrometry. The role of Cytochrome P3A4 (CYP3A4) enzymes in bromhexine metabolism was studied. Fungal incubates were spiked with reference standard - clarithromycin to confirm the role of CYP3A4 enzyme in bromhexine metabolism. Three metabolites appeared at 4.7, 5.5 and 6.4min retention time in HPLC. Metabolites produced by C. elegans and RLM were concluded to be similar based on their retention time, peak area and peak response of 30.05%, 21.06%, 1.34%, and 47.66% of three metabolites and bromhexine in HPLC. The role of CYP3A4 enzyme in metabolism of bromhexine and the presence of these enzymes in Cunninghamella species was confirmed due to absence of peaks at 4.7, 5.4 and 6.7min when RLM were incubated with a CYP3A4 enzyme inhibitor - clarithromycin. SN - 1678-4405 UR - https://www.unboundmedicine.com/medline/citation/27988088/Biotransformation_of_bromhexine_by_Cunninghamella_elegans_C__echinulata_and_C__blakesleeana_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27988088/ DB - PRIME DP - Unbound Medicine ER -