In vitro and ex vivo activity of thioridazine derivatives against Mycobacterium tuberculosis.
Thioridazine (TZ) has previously been shown by us to have in vitro and ex vivo activity against antibiotic-susceptible and multidrug-resistant Mycobacterium tuberculosis (MDRTB). Because current therapy of MDRTB is highly problematic even when all five 'first line of defence' drugs are employed, there is a need for effective antituberculosis drugs. New derivatives of TZ were synthesised and their in vitro activity against a reference strain of M. tuberculosis was evaluated with the aid of the BACTEC 460 system. Derivatives that presented significant activity were evaluated by ex vivo studies and were shown to enhance the killing of intracellular M. tuberculosis.
Martins
Marta
M
Unidade de Micobacterias, UPMM, Instituto de Higiene e Medicina Tropical, Universidade de Lisboa, Rua da Junqueira 96, 1394-008 Lisbon, Portugal.
Schelz
Zsuzsanna
Z
Martins
Ana
A
Molnar
Joseph
J
Hajös
Gyorgy
G
Riedl
Zsuzsanna
Z
Viveiros
Miguel
M
Yalcin
Ismail
I
Aki-Sener
Esin
E
Amaral
Leonard
L
D000995:Antitubercular Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010587:Phagocytosis; D013881:Thioridazine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000995:Antitubercular Agents; D013881:Thioridazine