Albaconazole

Toenail fungal infections account for half of all nail disease cases, and a highly negative impact on patient quality of life. Our aim was to compare the efficacy and safety of commercially available oral antifungals for onychomycosis.

A systematic review was performed in PubMed and Scopus. Randomized controlled trials evaluating the effect of oral antifungals on mycological cure, discontinuation and adverse events were included. Network meta-analyses were built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals (CrI). Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA).

We included 40 trials (n = 9568). Albaconazole 400 mg (OR 0.02 [95% CrI 0.01-0.07] versus placebo), followed by posaconazole 200-400 mg and terbinafine 250-350 mg were considered the best therapies (SUCRA probabilities over 75%). For the networks of discontinuation and individual adverse events, few significant differences among treatments were observed, but itraconazole 400 mg was considered the safest drug (SUCRA around 25%). Albaconazole 400 mg, posaconazole 200-400 mg, and terbinafine 250-350 mg were the most effective therapies for onychomycosis, while itraconazole 400 mg was the safest.

The profile of albaconazole and posaconazole compared to current first-line therapies should be further investigated in well-designed trials.

The data have been obtained for tautomers and enantiomers of ATTAF-1 and ATTAF-2 that were developed based on antifungal standard drugs with triazole scaffold. These compounds were docked into the human and fungal lanosterol-14α-demethylase. In order to validate the data, 8 standard triazole antifungal drugs (Fluconazole, Itraconazole, Posaconazole, Ravuconazole, Albaconazole, Voriconazole, Isavuconazole and Efinaconazole) were also docked into the human and fungal lanosterol-14α-demethylase. The binding conformations of these molecules and their interactions with lanosterol-14α-demethylase may inform the development of further small molecule lanosterol-14α-demethylase inhibitors with significant selectivity toward this enzyme. The analysis has done on the basis of type of interactions (bond type and distance). The length of the Fe-N coordination bond for (R)-N2-ATTAF-1 and (S)-N1-ATTAF-2 complexes is obtained 6.36 and 4.19 Å, respectively and about 2 Å in the other tautomer and enantiomer complexes, reflecting the lower basicity of the N-4 atom in the 1,2,4-triazole ring of (R)-N2-ATTAF-1 and (S)-N1-ATTAF-2 in comparison with the N-4 atom in the 1,2,4-triazole ring in other tautomers and enantiomers and supporting higher selectivity of (R)-N2-ATTAF-1 and (S)-N1-ATTAF-2 towards the target CYP51 enzymes vs. human. Interestingly, we have investigated unfavorable interactions (donor-donor) with TRP239 and MET378 for (R)-N2-ATTAF-1 and (S)-N1-ATTAF-2, respectively. These unfavorable interactions also have been seen in case of posaconazole and isavuconazole. The data presented in this article are related to the research paper entitled "In silico prediction of ATTAF-1 and ATTAF-2 selectivity towards human/fungal lanosterol 14α-demethylase using molecular dynamic simulation and docking approaches".