Etoposide and Camptothecin Reduce Growth, Viability, the Generation of Mutants, and Recognize the Active Site of DNA Topoisomerase I and II Enzymes in .

UNLABELLED

Candidemia, one of the most common invasive fungal infections in hospitalized patients, can lead to death and huge financial losses. is the main causative agent of this disorder and occupies the second or third place, for which new therapeutic alternatives must be found. The objective of the present study was to evaluate the inhibitory effect of etoposide and camptothecin (inhibitors of deoxyribonucleic acid (DNA) topoisomerase) on the CBS138 strain. Etoposide and camptothecin showed better or similar MIC (minimum inhibitory concentration) (5 and 2.5 μg/mL, respectively), with respect to fluconazole (8 μg/mL) and itraconazole (4 μg/mL). They also suppressed colony formation during the 12-h test. On the other hand, colonies were less formed by exposing to etoposide or camptothecin (indicating low toxicity), with respect fluconazole and itraconazole. Such colonies are phenotypically observed as limited growth in medium containing a non-fermentable carbon source, and are genotypically characterized by a partial or total loss of mitochondrial DNA (mtDNA) fragments. Using PCR techniques and cell staining with 4',6-diamidino-2-phenylindole (DAPI), loss of mtDNA was detected only in yeast cells treated with fluconazole. Additionally, molecular docking studies with etoposide and camptothecin showed recognition in the active site of the Topo I and II enzymes from . Since etoposide and camptothecin showed good inhibitory activity and low toxicity on ; they should certainly be of interest for the treatment of infections and the design and development of new antifungal compounds derived from these drugs.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12088-021-00942-6.