title: Activity of phosphino palladium(II) and platinum(II) complexes against HIV-1 and Mycobacterium tuberculosis.
abstract: Treatment of human immunodeficiency virus (HIV) is currently complicated by increased prevalence of co-infection with Mycobacterium tuberculosis. The development of drug candidates that offer the simultaneous management of HIV and tuberculosis (TB) would be of great benefit in the holistic treatment of HIV/AIDS, especially in sub-Saharan Africa which has the highest global prevalence of HIV-TB coinfection. Bis(diphenylphosphino)-2-pyridylpalladium(II) chloride (1), bis(diphenylphosphino)-2-pyridylplatinum(II) chloride (2), bis(diphenylphosphino)-2-ethylpyridylpalladium(II) chloride (3) and bis(diphenylphosphino)-2-ethylpyridylplatinum(II) (4) were investigated for the inhibition of HIV-1 through interactions with the viral protease. The complexes were subsequently assessed for biological potency against Mycobacterium tuberculosis H37Rv by determining the minimal inhibitory concentration (MIC) using broth microdilution. Complex (3) showed the most significant and competitive inhibition of HIV-1 protease (p = 0.014 at 100 µM). Further studies on its in vitro effects on whole virus showed reduced viral infectivity by over 80 % at 63 µM (p < 0.05). In addition, the complex inhibited the growth of Mycobacterium tuberculosis at an MIC of 5 µM and was non-toxic to host cells at all active concentrations (assessed by tetrazolium dye and real time cell electronic sensing). In vitro evidence is provided here for the possibility of utilizing a single metal-based compound for the treatment of HIV/AIDS and TB.
authors.affiliation: Department of Biochemistry, University of Pretoria, Hatfield Campus, Pretoria, 0002, South Africa.
authors.forename: Ntombenhle H
authors.initials: NH
authors.lastname: Gama
authors.affiliation: Department of Chemistry, University of Johannesburg, Kingsway Campus, Auckland Park, Johannesburg, 2006, South Africa.
authors.forename: Afag Y F
authors.initials: AY
authors.lastname: Elkhadir
authors.affiliation: DST/NRF Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand and the National Health Laboratory Service, P.O. Box 1038, Johannesburg, 2000, South Africa.
authors.forename: Bhavna G
authors.initials: BG
authors.lastname: Gordhan
authors.affiliation: DST/NRF Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand and the National Health Laboratory Service, P.O. Box 1038, Johannesburg, 2000, South Africa.
authors.forename: Bavesh D
authors.initials: BD
authors.lastname: Kana
authors.affiliation: Department of Chemistry, University of Johannesburg, Kingsway Campus, Auckland Park, Johannesburg, 2006, South Africa.
authors.forename: James
authors.initials: J
authors.lastname: Darkwa
authors.affiliation: Department of Biochemistry, University of Pretoria, Hatfield Campus, Pretoria, 0002, South Africa. dmeyer@uj.ac.za.|Dean's Office, Faculty of Science, University of Johannesburg, Kingsway Campus, Auckland Park, Johannesburg, 2006, South Africa. dmeyer@uj.ac.za.
authors.forename: Debra
authors.initials: D
authors.lastname: Meyer
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology; D010720:Phosphines / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D009942:Organometallic Compounds; D010720:Phosphines; D010984:Platinum; D010165:Palladium
keywords: HIV-1; Mycobacterium tuberculosis; Palladium complexes; Phosphine complexes; Platinum complexes