Abstract
We previously showed that microwave assisted synthesis is the best method for the synthesis of naphthoquinone amino acid and chloride-naphthoquinone amino acid derivatives by a complete evaluation of reaction conditions such as stoichiometry, bases, and pH influence. Following the same strategy, we synthesized chloride and non-chloride tyrosine, valine, and tryptophan-naphthoquinones achieving 85–95%, 80–92%, and 91–95% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone amino acid derivatives mainly display one redox reaction process. Overall, chloride naphthoquinone amino acid derivatives exhibited redox potential values (E1/2) more positive than non-chloride compounds. The six newly synthesized compounds were tested in HPV positive and negative as well as in immortal and tumorigenic cell lines to observe the effects in different cellular context simulating precancerous and cancerous status. A dose-response was achieved to determine the IC50 of six newly synthesized compounds in SiHa (Tumorigenic and HPV16 positive), CaLo (Tumorigenic and HPV18 positive), C33-A (Tumorigenic and HPV negative) and HaCaT (Keratinocytes immortal HPV negative) cell lines. Non-chloride tryptophan-naphthoquinone (3c) and chloride tyrosine-naphthoquine (4a) effects were more potent in tumorigenic SiHa, CaLo, and C33-A cells with respect to non-tumorigenic HaCaT cells. Interestingly, there seems to be a differential effect in non-chloride and chloride naphthoquinone amino acid derivatives in tumorigenic versus non tumorigenic cells. Considering all naphthoquinone amino acid derivatives that our group synthesized, it seems that hydrophobic and aromatic amino acids have the greatest effect on cell proliferation inhibition. These results show promising compounds for cervical cancer treatment.
Highlights
Naphthoquinones (NQ) are a group of natural and synthetic compounds known for their antibacterial, antifungal, anticancer, antimalarial, and antiviral effects, among others [1,2]
To complete the study of naphthoquinone amino acid derivatives against cancer cell lines, in this paper, we present the synthesis of valine, tyrosine and tryptophan 1,4-naphthoquinone (3a–c), and chloro-naphthoquinone (4a–c) derivatives by microwave (MAS) and irradiation, and their effect in the cervical cancer cell lines
A thorough understanding of the electron-transfer pathway is not considered in this work, the electrochemical studies of naphthoquinone amino acid derivatives give an insight of possible biological reactions concerning electron transfer processes that could occur at cellular level
Summary
Naphthoquinones (NQ) are a group of natural and synthetic compounds known for their antibacterial, antifungal, anticancer, antimalarial, and antiviral effects, among others [1,2]. Several studies have reported that naphthoquinones with different substituents like paclitaxel, esters, metals, furans, carbazoles, or inclusive with carbohydrates in their structure, among others, inhibit cell proliferation [3,4,5] These properties are principally attributed to the oxidant-reductive characteristics of naphthoquinones, which allow the generation of dianions or semiquinone radicals. ROS generation with naphthoquinones represents a challenge in the design of new active compounds, principally with anticancer effects In this context, the addition/substitution on naphthoquinone moiety by atoms or groups such as flour, oxygen, or amine can be modulated by redox properties, decreasing the toxicity levels and maintaining or potentiating the biological effect [12,13,14]
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