Antifungal Constituents of Piper crocatum and Their Activities as Ergosterol Biosynthesis Inhibitors Discovered via In Silico Study Using ADMET and Drug-Likeness Analysis

Abstract

Along with the increasing resistance of Candida spp. to some antibiotics, it is necessary to find new antifungal drugs, one of which is from the medicinal plant Red Betel (Piper crocatum). The purpose of this research is to isolate antifungal constituents from P. crocatum and evaluate their activities as ergosterol biosynthesis inhibitors via an in silico study of ADMET and drug-likeness analysis. Two new active compounds 1 and 2 and a known compound 3 were isolated, and their structures were determined using spectroscopic methods, while their bioactivities were evaluated via in vitro and in silico studies, respectively. Antifungal compound 3 was the most active compared to 1 and 2 with zone inhibition values of 14.5, 11.9, and 13.0 mm, respectively, at a concentration of 10% w/v, together with MIC/MFC at 0.31/1.2% w/v. Further in silico study demonstrated that compound 3 had a stronger ΔG than the positive control and compounds 1 and 2 with −11.14, −12.78, −12.00, and −6.89 Kcal/mol against ERG1, ERG2, ERG11, and ERG24, respectively, and also that 3 had the best Ki with 6.8 × 10−3, 4 × 10−4, 1.6 × 10−3, and 8.88 μM. On the other hand, an ADMET analysis of 1–3 met five parameters, while 1 had one violation of Ro5. Based on the research data, the promising antifungal constituents of P. crocatum allow P. crocatum to be proposed as a new antifungal candidate to treat and cure infections due to C. albicans.

Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper crocatum Ruiz & Pav

“…It can be considered as a new treatment option for C. albicans infections, with a mechanism of action similar to that of azole antibiotics, by inhibiting fungal ergosterol. 82 The three components’ structure is as illustrated in Figure 9 .

Figure 9 Structure of antifungal constituents of P. crocatum , Piperyamide A ( 33 ), Piperyamine A ( 34 ), and Stigmasterol ( 35 ).

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Figure 9 Structure of antifungal constituents of P. crocatum , Piperyamide A ( 33 ), Piperyamine A ( 34 ), and Stigmasterol ( 35 ). 82

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The prospects of complementary treatment using Red Piper betle (Piper crocatum) against leucorrhoea: an empirical study

“…The treatment in the form of using boiled and soaked P. crocatum leaves was prepared and carried out by midwives and cadres to the respondents, so that the respondents and researchers did not know whether the treatment received was in the form of boiled or soaked P. crocatum leaves. Determination of the sample size using the Federer formula as follows (Siswina et al, 2023):…”

“…Therefore, alternative non-pharmacological treatments based on natural products are needed. P. crocatum as a natural product has analgesic, antimicrobial, antioxidant, antifungal, and anti-inflammatory activities according to ethnopharmacology data with 677 known compounds (Alfiana et al, 2022;Saputra et al, 2016;Siswina et al, 2023). P. crocatum contains secondary metabolites such as flavonoids (1), alkaloids (2), triterpenoids or steroids (3), hydroxychavicol (4), tannin (5), saponins (6), terpenes, and phenolics (Fig 1) (Erviana, 2011;Gutierrez et al, 2013).…”