Design, Synthesis, and Biological Evaluation of Some Novel Retinoid Derivatives
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bentham Science Publishers
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background: As cancer stands as a significant global health concern, many heterocyclic compounds that are more effective in cancer cells than healthy cells are being investigated for their selective anticancer potentials. One such compound is fenretinide, a synthetic derivative of retinoic acid that has a broad spectrum of cytotoxic activity against primary tumor cells, cell lines, and/or xenografts of various cancers. In this context, bexarotene and its derivatives, synthesized from hybridization of the fenretinide, are expected to possess a potential anticancer activity. Objective: The objective of the present study was to investigate the synthesis of novel amid-derived and bexarotene-based compounds, as well as to assess their cytotoxic effects in different cancer cell lines. Methods: This study involved the synthesis of twelve novel retinoid derivatives (6-17) in a six-step process. The cytotoxic activities of these compounds were assessed against various cancer cell lines, such as A549 (human lung carcinoma), HeLa (human cervical cancer), MCF7 (human breast adenocar-cinoma), and WiDr (human colon adenocarcinoma). The chemical structures of these compounds were elucidated through their elemental analysis, mass spectrometry (ESI+, ESI-), as well as1H-NMR and13C-NMR spectroscopic data. Results: The obtained cell toxicity results indicated that compounds 6, 8, 11, 12, 13, 14, and 17 were found to exhibit the strongest cytotoxic activity in above mentioned cancer cell lines. The IC50 values for active compounds, 11 and 12, were determined as 2.38µM and 2.29µM, respectively. Remarkably, these compounds displayed higher cytotoxic activity in the WiDr cell line related to positive control, camptothecin (CPT). Moreover, compounds 14 and 17 demonstrated very similar level of cytotoxic activity to CPT, indicating their potential for antitumoral applications upon further studies. Conclusion: While compounds 11, 12, 14, and 17 indicated a very comparable anticancer activity to CPT, compounds 6, 8, 11 and 12 showed more selective anticancer effect against cancer cells than non-cancerous cells. In accordance with the findings of the present study, they can be evaluated as primary candidates for further studies, specifically as RXRα-targeted anticancer agents. © 2024 Bentham Science Publishers.
Açıklama
Anahtar Kelimeler
Anticancer, Bexarotene, Cytotoxicity, Hybrid Molecules, Retinoid, RXRa
Kaynak
Letters in Drug Design and Discovery
WoS Q Değeri
Q4
Scopus Q Değeri
Q3
Cilt
21
Sayı
14
Künye
Konyar, D., Foto, E., Foto, F. Z., & Buyukbingol, M. E. (2024). Design, Synthesis, and Biological Evaluation of Some Novel Retinoid Derivatives. Letters in Drug Design & Discovery, 21(14), 2926-2938.
