title: Alkaloid extracts from Combretum zeyheri inhibit the growth of Mycobacterium smegmatis.
abstract: BACKGROUND
  Current tuberculosis regimens have failed to combat the issue of drug resistance and ethno medicines may represent a possible source of antimycobacterial agents. Combretum species are well known in African traditional medicines and used for various ailments including pneumonia, venereal diseases like syphilis, mental problems, relief of sore throats and colds, fever, and chest coughs associated with tuberculosis. Alkaloids function as either hydrogen-acceptor or hydrogen-donor in hydrogen bonding critical for the interaction between targets thus, potentiating effects of curative agents on diseases. Alkaloid extracts from leaves of Combretum zeyheri, Combretum platypetalum, Combretum molle and Combretum apiculatum, were assessed for antimycobacterial activity to establish rationale for their use in traditional medicines for various ailments including pneumonia, relief of sore throats and colds, fever, and chest coughs associated with tuberculosis.
  
  
  METHODS
  Alkaloids were extracted from the leaves of Combretum zeyheri, Combretum platypetalum, Combretum molle and Combretum apiculatum. The broth microdilution method was used for the screening of growth inhibitory activity. The standard drug rifampicin was used as the positive control. Alkaloid extracts from the most potent plant species, Combretum zeyheri were further investigated for time-kill dependency effects on drug transport in Mycobacterium smegmatis.
  
  
  RESULTS
  Using the broth microdilution susceptibility method, C. zeyheri alkaloid extract, was found to have the most antimycobacterial effects with an MIC value of 125 μg/ml whilst MICs for C. molle and C. platypetalum were above 1000 μg/ml. An MBC value of 250 μg/ml was observed with alkaloid extracts from Combretum zeyheri whilst the remaining three Combretum species showed no bactericidal activity. It was also shown that C. zeyheri had potential efflux pump inhibitory activity. Determination of the time-kill kinetics of extracts from C. zeyheri showed not only a concentration-dependent activity but time-dependent bactericidal effect as well.
  
  
  CONCLUSIONS
  Alkaloid extracts from the leaves of C. zeyheri have potential as a source of lead compounds that may be developed further into antimycobacterial compounds. The mechanism of action of may be due to inhibition of transport across the cell membrane. Further work needs to be done to isolate the active components in these extracts.
authors.affiliation: School of Pharmacy, College of Health Sciences, University of Zimbabwe, Mt. Pleasant, Harare, Zimbabwe.
authors.forename: Tafadzwa
authors.initials: T
authors.lastname: Nyambuya
authors.affiliation: Department of Biochemistry, University of Zimbabwe, P.O. Box MP 167, Mt. Pleasant, Harare, Zimbabwe.
authors.forename: Ruvimbo
authors.initials: R
authors.lastname: Mautsa
authors.affiliation: Department of Biochemistry, University of Zimbabwe, P.O. Box MP 167, Mt. Pleasant, Harare, Zimbabwe. smukanganyama@medic.uz.ac.zw.
authors.forename: Stanley
authors.initials: S
authors.lastname: Mukanganyama
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D029765:Combretum / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000254:growth & development; D010936:Plant Extracts / Q000494:pharmacology*; D015030:Zimbabwe
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D010936:Plant Extracts
keywords: Alkaloid extracts; Combretum species; Drug efflux; Drug susceptibility test; Mycobacterium smegmatis