title: Antibacterial and cytotoxic cytochalasins from the endophytic fungus Phomopsis sp. harbored in Garcinia kola (Heckel) nut.
abstract: BACKGROUND
  The continuous emergence of multidrug-resistant (MDR) bacteria drastically reduced the efficacy of our antibiotic armory and consequently, increased the frequency of therapeutic failure. The search for bioactive constituents from endophytic fungi against MDR bacteria became a necessity for alternative and promising strategies, and for the development of novel therapeutic solutions. We report here the isolation and structure elucidation of antibacterial and cytotoxic compounds from Phomopsis sp., an endophytic fungus associated with Garcinia kola nuts.
  
  
  METHODS
  The fungus Phomopsis sp. was isolated from the nut of Garcinia kola. The crude extract was prepared from mycelium of Phomopsis sp. by maceration in ethyl acetate and sequentially fractionated by column chromatography. The structures of isolated compounds were elucidated on the basis of spectral studies and comparison with published data. The isolated compounds were evaluated for their antibacterial and anticancer properties by broth microdilution and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods respectively. The samples were also tested spectrophotometrically for their hemolytic properties against human red blood cells.
  
  
  RESULTS
  The fractionation of the crude extract afforded three known cytochalasins including 18-metoxycytochalasin J (1), cytochalasins H (2) and J (3) together with alternariol (4). The cytochalasin compounds showed different degrees of antibacterial activities against the tested bacterial pathogens. Shigella flexneri was the most sensitive microorganism while Vibrio cholerae SG24 and Vibrio cholerae PC2 were the most resistant. Ampicillin did not show any antibacterial activity against Vibrio cholerae NB2, Vibrio cholerae PC2 and Shigella flexneri at concentrations up to 512 μg/mL, but interestingly, these multi-drug resistant bacterial strains were sensitive to the cytochalasin metabolites. These compounds also showed significant cytotoxic properties against human cancer cells (LC50= 3.66-35.69 μg/mL) with low toxicity to normal non-cancer cells.
  
  
  CONCLUSIONS
  The three cytochalasin compounds isolated from the Phomopsis sp. crude extract could be a clinically useful alternative for the treatment of cervical cancer and severe infections caused by MDR Shigella and Vibrio cholerae.
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon.
authors.forename: Jean-Bosco
authors.initials: JB
authors.lastname: Jouda
authors.affiliation: Department of Biochemistry, Faculty of Science, Laboratory of Microbiology and Antimicrobial Substances, University of Dschang, P.O. Box 67, Dschang, Cameroon. jtamokou@yahoo.fr.|Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India. jtamokou@yahoo.fr.
authors.forename: Jean-de-Dieu
authors.initials: JD
authors.lastname: Tamokou
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon. djamaceline@yahoo.com.
authors.forename: Céline Djama
authors.initials: CD
authors.lastname: Mbazoa
authors.affiliation: Julius Kühn Institut, Federal Research Centre for Cultivated Plants, Institute for National and International Plant Health, Messeweg 11-12, D-38104, Braunschweig, Germany.
authors.forename: Clovis
authors.initials: C
authors.lastname: Douala-Meli
authors.affiliation: Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India.
authors.forename: Prodipta
authors.initials: P
authors.lastname: Sarkar
authors.affiliation: Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India.
authors.forename: Prasanta Kumar
authors.initials: PK
authors.lastname: Bag
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon.
authors.forename: Jean
authors.initials: J
authors.lastname: Wandji
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003572:Cytochalasins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029763:Garcinia kola / Q000382:microbiology*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009754:Nuts / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D003572:Cytochalasins
keywords: Antibacterial; Cytochalasins; Cytotoxic; Endophytic fungi; Garcinia kola; Metabolites; Phomopsis sp