Experimental in vitro Efficacy Study on the Interaction of Epiroprim plus Isoniazid against <i>Mycobacterium tuberculosis</i>

Abstract

Thirty Mycobacterium tuberculosis strains (8: INH^R/INH^R, 12: INH^R/RIF^S, 10: INH^S/RIF^S) were examined against MICs of epiroprim (EPM) and isoniazid (INH) separately or in association. EPM alone proved to be insufficiently active against the various mycobacterial isolates (MIC ≧256 µg/ml). The observed average sensitivity to the association of EPM plus INH was, in contrast, considerably increased, as reflected by reduced MICs and lower percentages of resistant strains. MICs ranged between 16 and 32 µg/ml EPM and 2 and 4 µg/ml INH for INH^R strains. All INH^S isolates were inhibited by a concentration of 0.125 µg/ml EPM and 0.06 µg/ml INH. The fractional inhibitory concentration indices indicated an additive activity on INH^R/RIF^R strains and a synergistic activity on INH^R/RIF^S and INH^S/RIF^S strains. The synergistic activity of this drug association needs to be confirmed in an animal model.

Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin

“…Isobologram analysis is the most accepted and rigorous method for evaluating drug interactions in combination mixtures and employed in other studies, e.g. cancer [ 30 ], tuberculosis [ 31 ] inflammation [ 32 ] or malaria [ 7 , 8 , 33 , 34 ]. Interaction studies for both the plant extracts among themselves (AP+HC) and with curcumin individually (AP+CUR, HC+CUR), at four fixed ratios (1:5, 1:2, 2:1 and 5:1) were carried out in vitro on a chloroquine-resistant isolate of P. falciparum (MRC-pf-303).…”

Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors

“…One of used drug, Epiroprim (Ro 11-8958) ( Fig. 5) has recently been evaluated against various M. tuberculosis and found to exhibit weak activity [121]. In turn, Queener et al [122], as well as Then et al [123], based on potency and selectivity tests toward purified recombinant pcDHFR, have suggested, that Ro 11-8958 was the strongest inhibitor among the series of their TMP analogues.…”