Characterization of the Cytotoxic Effect of Naphthalenacetamides Hydrochlorides on Cervical Cancer-Derived Cells
Cristina Martinez-Nava1, Cuauhtemoc Perez-Gonzalez2, Miguel Ángel Zavala-Sanchez2
1Department of Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Ciudad de México, México.
Introduction:
Cervical cancer is a global health problem due to its high incidence and prevalence in women, mainly in third-world countries. For the treatment of this disease, there are different therapeutic options, but these are not always effective, which gives rise to the search for new compounds using cheminformatics tools.
Objective:
The objective of this study was to design, synthesize, and biologically evaluate N-(2- morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide hydrochloride (1) and 2-(naphthalen-2-yloxy)- N-(2-(piperidin-1-yl)ethyl)acetamide hydrochloride (2) on the HeLa cell line in vitro. The referenced cell line from the American Type Culture Collection (ATCC®CCL-2™) was used, and the effect on cell viability was determined by MTT metabolic reduction-based assay at 24, 48, and 72 h.
Methods:
Therapies directed at the σ1 receptor may be a treatment alternative since this receptor modulates the processes of cell proliferation and angiogenesis, producing cytoprotective or cytotoxic actions depending on the ligand with which it is coupled.
Results:
The analysis showed that compounds 1 and 2 presented activity on HeLa cancer cells and viability at micromolar concentrations (1.923 μmol/mL and 0.374 μmol/mL, respectively). Moreover, the effect was maintained for 72 h.
Conclusion:
Naphthaleneacetamide derivatives exhibited an inhibitory effect on the HeLa cell line, and the OSIRIS program predicted less toxicity than cisplatin.
Insights
New naphthaleneacetamide derivatives show promise in inhibiting cervical cancer cells. These compounds demonstrated significant activity against the HeLa cell line in vitro, with potential for reduced toxicity compared to existing treatments.
Area of Science:
- Medicinal Chemistry
- Oncology
- Pharmacology
Background:
- Cervical cancer poses a significant global health challenge, particularly in developing nations.
- Existing therapeutic options for cervical cancer have limitations, necessitating the exploration of novel compounds.
- Cheminformatics tools are instrumental in the discovery of new therapeutic agents.
Purpose of the Study:
- To design, synthesize, and evaluate the in vitro biological activity of two novel naphthaleneacetamide derivatives.
- To assess the efficacy of compounds N-(2-morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide hydrochloride (1) and 2-(naphthalen-2-yloxy)-N-(2-(piperidin-1-yl)ethyl)acetamide hydrochloride (2) against the HeLa cervical cancer cell line.
- To determine the impact of these compounds on cell viability over 24, 48, and 72 hours.
Main Methods:
- Synthesis of naphthaleneacetamide derivatives.
- In vitro biological evaluation using the HeLa cell line (ATCC® CCL-2™).
- Assessment of cell viability via MTT metabolic reduction assay at multiple time points.
Main Results:
- Compounds 1 and 2 exhibited significant inhibitory activity against HeLa cancer cells at micromolar concentrations.
- Specific activity levels were recorded at 1.923 μmol/mL for compound 1 and 0.374 μmol/mL for compound 2.
- The observed cytotoxic effect was sustained for up to 72 hours.
Conclusions:
- Naphthaleneacetamide derivatives demonstrate a notable inhibitory effect on the HeLa cell line.
- Computational analysis using the OSIRIS program suggests these compounds may possess lower toxicity than cisplatin.
- These findings highlight the potential of naphthaleneacetamide derivatives as novel therapeutic agents for cervical cancer.
