Abstract
It was found that the effect of Ca, Cu, Ni, Fe (III), Al, Hg, Mg, Zn, Mn, Cd, and Co (II) on the in vitro action of PAS, INAH, TBI, SM, and DHSM against sensitive and resistant strains of human-type tubercle bacilli and the presence or absence of tendency of these metallic ions to form a complex with these antitubercular agents were in parallel relation. This suggests the role of complex formation in the mechanism of these metals affecting the in vitro action of antitubercular agents. As was pointed out earlier, the effect of metals cannot be explained by the direct action of the metal on tubercle bacilli or the toxic action of the metal complex itself. In this connection, a hypothesis has been presented on the effect of metals on the in vitro action of these antitubercular agents. The antitubercular action of these agents seems to be displayed in connection with a requisite metal in an enzyme. When a metal forms a complex salt with a substance which competes with the antitubercular agent for this particular metal, a synergism between a metal and the agent occurs, but when the antitubercular agent and the said metal forms a complex salt, then antagonism occurs. Which complex is formed depends on the stability of the complex. This hypothesis can well explain the facts observed and reported in Parts I and II of this series.
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