title: Studies on the mode of action of tolnaftate in Microsporum gypseum.
abstract: Studies were performed on the mode of action of tolnaftate and resistance to this drug in Microsporum gypseum. Cells grown in the presence of tolnaftate (at the IC 50) showed a reduced content of total phospholipids and sterols whereas there was an increase in total RNA content. Incubation of cells with tolnaftate (at 10 x MIC), followed by addition of different macromolecule precursors revealed inhibition of the biosynthesis of all macromolecules except for RNA. The activity of membrane-bound enzymes did not change on treatment with tolnaftate (10 x MIC) whereas an increase in the leakage of intracellular 32P was observed. The content of total phospholipids was higher in tolnaftate-resistant cells, whereas the content of total sterols, DNA, RNA and protein was comparable to that of susceptible cultures. Activity of phosphodiesterase decreased and 5'-nucleotidase increased in tolnaftate-resistant cells. Our results suggest that the antifungal activity of tolnaftate is due to differential action on various targets site(s) which are modified in strains resistant to the drug.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Candigarh, India.
authors.forename: M P
authors.initials: MP
authors.lastname: Gupta
authors.forename: N
authors.initials: N
authors.lastname: Kapur
authors.forename: I
authors.initials: I
authors.lastname: Bala
authors.forename: G K
authors.initials: GK
authors.lastname: Khuller
mesh_terms: D004271:DNA, Fungal / Q000032:analysis / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000032:analysis / Q000096:biosynthesis; D008864:Microsporum / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D010743:Phospholipids / Q000032:analysis / Q000096:biosynthesis; D012331:RNA, Fungal / Q000032:analysis / Q000096:biosynthesis; D013261:Sterols / Q000032:analysis / Q000096:biosynthesis; D014047:Tolnaftate / Q000494:pharmacology*
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D010743:Phospholipids; D012331:RNA, Fungal; D013261:Sterols; D014047:Tolnaftate