Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells

Gülşah Karakaya; Ayşe Ercan; Selin Öncül; Mutlu Aytemir

Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells

Abstract

Malignant melanoma is a serious type of skin cancer with high mortality rates, arising from melanocytic cells responsible for the pigmentation of the skin. Besides, the excessive accumulation of melanin pigment can lead to many other hyperpigmentation disorders. Kojic acid is used as a skin lightening agent of medicinal and cosmetic products used in hyperpigmentation and sunburn cases. In the present study, substituted halogen containing benzylpiperazine derivatives of kojic acid (compounds 1-9) were synthesized via Mannich reaction in mild conditions. Afterwards, the cyclic amine derivatives (compounds 10-26) were obtained as a result of nucleophilic substitutions. Cytotoxic effects of all the compounds on A375 human malignant melanoma cell lines were explored by sulphorhodamine B assay and efficacies has been compared to those of anticancer FDA-approved drugs dacarbazine, temozolomide, and lenalidomide, currently used in the treatment of malignant melanoma. Also, the most active two compounds were also tested on healthy cell lines (HGF-1 and MRC-5 cell lines). These compounds have shown highest activity (IC50: 71.27 for compound 9 and 73.74 µM for compound 1) than temozolomide (IC50: 95.6 µM) and lenalidomide (IC50: 143.1 µM) against A375 cells though giving less harm to non-cancerous cell lines. In conclusion, these compounds stand out as promising anticancer agents for further studies.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Gülşah Karakaya
Türkiye

Ayşe Ercan
Türkiye

Selin Öncül This is me
Türkiye

Mutlu Aytemir ^*
Türkiye

Publication Date

June 27, 2025

Submission Date

February 18, 2019

Acceptance Date

May 29, 2019

Published in Issue

Year 2019 Volume: 23 Number: 4

IZ

https://izlik.org/JA88WB28KJ

Cite

RIS / Bibtex

APA

Karakaya, G., Ercan, A., Öncül, S., & Aytemir, M. (2025). Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells. Journal of Research in Pharmacy, 23(4), 596-607. https://izlik.org/JA88WB28KJ

AMA

1.Karakaya G, Ercan A, Öncül S, Aytemir M. Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells. J. Res. Pharm. 2025;23(4):596-607. https://izlik.org/JA88WB28KJ

Chicago

Karakaya, Gülşah, Ayşe Ercan, Selin Öncül, and Mutlu Aytemir. 2025. “Kojic Acid Derivatives As Potential Anticancer Agents: Synthesis and Cytotoxic Evaluation on A375 Human Malignant Melanoma Cells”. Journal of Research in Pharmacy 23 (4): 596-607. https://izlik.org/JA88WB28KJ.

EndNote

Karakaya G, Ercan A, Öncül S, Aytemir M (June 1, 2025) Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells. Journal of Research in Pharmacy 23 4 596–607.

IEEE

[1]G. Karakaya, A. Ercan, S. Öncül, and M. Aytemir, “Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells”, J. Res. Pharm., vol. 23, no. 4, pp. 596–607, June 2025, [Online]. Available: https://izlik.org/JA88WB28KJ

ISNAD

Karakaya, Gülşah - Ercan, Ayşe - Öncül, Selin - Aytemir, Mutlu. “Kojic Acid Derivatives As Potential Anticancer Agents: Synthesis and Cytotoxic Evaluation on A375 Human Malignant Melanoma Cells”. Journal of Research in Pharmacy 23/4 (June 1, 2025): 596-607. https://izlik.org/JA88WB28KJ.

JAMA

1.Karakaya G, Ercan A, Öncül S, Aytemir M. Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells. J. Res. Pharm. 2025;23:596–607.

MLA

Karakaya, Gülşah, et al. “Kojic Acid Derivatives As Potential Anticancer Agents: Synthesis and Cytotoxic Evaluation on A375 Human Malignant Melanoma Cells”. Journal of Research in Pharmacy, vol. 23, no. 4, June 2025, pp. 596-07, https://izlik.org/JA88WB28KJ.

Vancouver

1.Gülşah Karakaya, Ayşe Ercan, Selin Öncül, Mutlu Aytemir. Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells. J. Res. Pharm. [Internet]. 2025 Jun. 1;23(4):596-607. Available from: https://izlik.org/JA88WB28KJ