Gallic Acid Derived 1, 2-Diarylindole as a Potential Antifungal Agent against Candida Strain.

Autor:	Kurmi A; Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India., Singh AP; CSIR-Institute of Genomics and Integrative Biology (IGIB), Mathura Road, New Delhi, 110025, India., Gautam Y; Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow, 226 015, Uttar Pradesh, India.; Department of Chemistry, Pandit Prithi Nath PG College, 96/12, Mahatma Gandhi Marg, Kanpur, 208001, Uttar Pradesh, India., Singh N; Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.; Department of Pharmaceutical Sciences, Hemvati Nandan Bahuguna Garhwal University Srinagar, 246174, Uttarakhand, India., Tripathi A; Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India., Negi AS; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India.; Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow, 226 015, Uttar Pradesh, India., Gautam HK; CSIR-Institute of Genomics and Integrative Biology (IGIB), Mathura Road, New Delhi, 110025, India., Pal A; Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India., Saikia D; Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India.
Jazyk:	angličtina
Zdroj:	Current topics in medicinal chemistry [Curr Top Med Chem] 2024 Feb 15. Date of Electronic Publication: 2024 Feb 15.
DOI:	10.2174/0115680266278892240102045630
Abstrakt:	Background: In recent decades, Candida albicans 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)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1- amine (7, 100DL-6) by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (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)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (7, 100DL-6) was done by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS-Delhi). Compound 100DL-6 efficacy was determined by Combination synergy study, ergosterol binding assay, MTT toxicity study and Mutagenicity. Results: Compound 100DL-6 was obtained in 65% yield on desired motifs. Docking scores found were 100DL-6 (-8.7 kcal/mol) and Fluconazole (-7.6 kcal/mol). Further, RMSD were shown for 100DL6 (0.26 ± 0.23 nm) and fluconazole (1.2 ± 0.62 nm). Indole derivative 100DL-6 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 100DL-6 with known antifungal drugs was observed. In the presence of ergosterol 100DL-6 and standard drug (s) increased their MIC values, demonstrating a considerable affinity for ergosterol. Compound 100DL-6 was considered to be less-cytotoxic to the cells as determined by MTT assay. Lead compound 100DL-6 was found to be non-mutagenic. Conclusion: In the present study, 100DL6 (indole derivatives) significantly abrupted the ergosterol biosynthetic pathway and showed moderate anti-candidal effects. These studies suggest that 100DL6 significantly enhances antifungal effect of clinical drug fluconazole synergistically and may be considered as in clinical trial prior to some extensive in-vivo validations. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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