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2000
Volume 25, Issue 9
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Background

In recent decades, has become a serious issue for public health. The worldwide rapid rise in drug resistance to conventional therapies is the main contributing reason. Moreover, because of their potent activity at low concentrations and apparent lack of toxicity, compounds originating from plants are used in therapeutic treatments because of their potent activity at low concentrations and apparent lack of toxicity. Particularly in immunocompromised people, Candida species can result in a wide range of ailments.

Objectives

Present manuscript describes antifungal activity of an indole derivative 1-(4-((5-methoxy-2-(3,4,5-trimethoxyphenyl)-1-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (, ) by using and anti-candidal activity against two Candida strains; -DS-02 (ATCC-204093) and (AI-clinical isolate, AIIMS-Delhi).

Methods

The synthetic strategy for the preparation of indole derivatives was modified through Fischer indole reaction. Antifungal activity of an indole derivative 1-(4-((5-methoxy-2-(3,4,5-trimethoxyphenyl)-1-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (, ) was done by using and anti-candidal activity against two Candida strains; -DS-02 (ATCC-204093) and (AI-clinical isolate, AIIMS-Delhi). Compound efficacy was determined by Combination synergy study, ergosterol binding assay, MTT toxicity study and Mutagenicity.

Results

Compound was obtained in 65% yield on desired motifs. Docking scores found were (-8.7 kcal/mol) and Fluconazole (-7.6 kcal/mol). Further, RMSD were shown for (0.26 ± 0.23 nm) and fluconazole (1.2 ± 0.62 nm). Indole derivative was active against the tested fungal pathogens and the total zone of inhibition was measured between 13-14 mm in diameter and MIC values between 31.25 μg/mL to 250 μg/mL and MFC values between 62.5 μg/mL to 500 μg/mL. In checkerboard assay synergistic mode of interaction of with known antifungal drugs was observed. In the presence of ergosterol and standard drug (s) increased their MIC values, demonstrating a considerable affinity for ergosterol. Compound was considered to be less-cytotoxic to the cells as determined by MTT assay. Lead compound was found to be non-mutagenic.

Conclusion

In the present study, (indole derivatives) significantly abrupted the ergosterol biosynthetic pathway and showed moderate anti-candidal effects. These studies suggest that significantly enhances antifungal effect of clinical drug fluconazole synergistically and may be considered as in clinical trial prior to some extensive validations.

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Gallic Acid Derived 1, 2-Diarylindole as a Potential Synergistic Antifungal Agent against Candida Strains
Curr. Top. Med. Chem. 25, 999 (2025); https://doi.org/10.2174/0115680266278892240102045630
/content/journals/ctmc/10.2174/0115680266278892240102045630
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  • Article Type:     Research Article
Keyword(s): Anti-candidal; Docking; MD simulation; MIC; Synergistic assay; Zone of inhibition

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