Design, Synthesis, and Biological Evaluation of Some Novel Retinoid Derivatives

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. background: Cancer is currently the most prevalent disease. It is already known that the Fenretinide compound shows biological activity template. The Fenretinide compound is obtained as a result of the amidification of the retinoic acid with p-hydroxy aniline. The Bexarotene compound and its derivatives that will be obtained as a result of the hybridization of the Fenretinide compound are expected to show 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. objective: The purpose of this study was to analyze the synthesis of novel amid-derived compounds based on Bexarotene and cytotoxic effects in different cancer tissues. 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 adenocarcinoma), and WiDr (human colon adenocarcinoma). The chemical structures of these compounds were elucidated through their elemental analysis, mass spectrometry (ESI+, ESI-), as well as 1H-NMR and 13C-NMR spectroscopic data. method: In this study, novel twelve retinoid derivatives (6-17) were synthesized in six steps. Cytotoxic activities of the compounds have been tested against human lung carcinoma cells (A549), human cervical cancer cells (HeLa), human breast adenocarcinoma (MCF7), and human colon adenocarcinoma cell line (WiDr). The chemical structures of the compounds were explained with their elemental analysis, mass (ESI+, ESI-), and 1H-NMR, 13C-NMR spectral 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. result: According to the obtained cytotoxicity results, compounds 6, 8, 11, 12, 13, 14, and 17 were found to have the highest cytotoxic activity in 4 cancer cell lines. The IC 50 values for active compounds, 11 and 12 were shown as 2,38µM; and 2,29µM, respectively, and these compounds were determined higher cytotoxic activity in the WiDr colon cancer cell line than as a positive control CPT. The closest activity as a positive control CPT was observed in compounds 14 and 17 have the potential for antitumoral applications following further analysis. 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 noncancerous 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. other: Objective: The purpose of this study was to analyze the synthesis of novel amid-derived compounds based on Bexarotene and cytotoxic effects in different cancer tissues. Background: Cancer is currently the most prevalent disease. It is already known that the Fenretinide compound shows biological activity template. The Fenretinide compound is obtained as a result of the amidification of the retinoic acid with p-hydroxy aniline. The Bexarotene compound and its derivatives that will be obtained as a result of the hybridization of the Fenretinide compound are expected to show anticancer activity. Methods: In this study, novel twelve retinoid derivatives (6-17) were synthesized in six steps. Cytotoxic activities of the compounds have been tested against human lung carcinoma cells (A549), human cervical cancer cells (HeLa), human breast adenocarcinoma (MCF7), and human colon adenocarcinoma cell line (WiDr). The chemical structures of the compounds were explained with their elemental analysis, mass (ESI+, ESI-), and 1H-NMR, 13C-NMR spectral data. Results: According to the obtained cytotoxicity results, compounds 6, 8, 11, 12, 13, 14, and 17 were found to have the highest cytotoxic activity in 4 cancer cell lines. The IC 50 values for active compounds, 11 and 12 were shown as 2,38µM; and 2,29µM, respectively, and these compounds were determined higher cytotoxic activity in the WiDr colon cancer cell line than as a positive control CPT. The closest activity as a positive control CPT was observed in compounds 14 and 17 have the potential for antitumoral applications following further analysis. Conclusion: Considering the results in this study, the closest activity as a positive control CPT was observed in compounds 11, 12, 14, and 17 can be used as the lead compounds targeting RXRα for anticancer compounds for further studies.