Abstract
We performed an extensive analysis about the reaction conditions of the 1,4-Michael addition of amino acids to 1,4-naphthoquinone and substitution to 2,3-dichloronaphthoquinone, and a complete evaluation of stoichiometry, use of different bases, and the pH influence was performed. We were able to show that microwave-assisted synthesis is the best method for the synthesis of naphthoquinone–amino acid and chloride–naphthoquinone–amino acid derivatives with 79–91% and 78–91% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone–amino acid derivatives mainly display one quasi-reversible redox reaction process. Interestingly, it was shown that naphthoquinone derivatives possess a selective antitumorigenic activity against cervix cancer cell lines and chloride–naphthoquinone–amino acid derivatives against breast cancer cell lines. Furthermore, the newly synthetized compounds with asparagine–naphthoquinones (3e and 4e) inhibited ~85% of SiHa cell proliferation. These results show promising compounds for specific cervical and breast cancer treatment.
Highlights
Naphthoquinone (NQ) is a nucleus found in several natural and synthetic compounds that offers several applications, such as pigments, and many biological properties, including antibacterial, antifungal, anticancer, antimalarial, and antiviral, among others [1,2]
We present the synthesis of a series of 1,4-naphthoquinone–amino acid (3a–e) and 2,3-dichloronaphhtoquinone (4a–4e) derivatives under several activation methods, such as room temperature synthesis (RTS), reflux synthesis (RS), microwave-assisted synthesis (MAS), and ultrasound-assisted synthesis (UAS), and determined the effectivity on the system
In a general method to prepare 3a–e derivatives, the corresponding amino acid 2a–c was added in a 1,4-type bond form to the naphthoquinone 1a, using initially, the conditions reported in the literature (Figure 1) [19,23]
Summary
Naphthoquinone (NQ) is a nucleus found in several natural and synthetic compounds that offers several applications, such as pigments, and many biological properties, including antibacterial, antifungal, anticancer, antimalarial, and antiviral, 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, present effects of diminishing cell proliferation [3,4,5]. These properties are principally attributed to the oxidant-reductive characteristics of the naphthoquinones, which allow the generation of dianions or semiquinone radicals. Cell proliferation inhibition could be achieved by the induction of apoptosis, topoisomerase II-α inhibition, and ROS generation, among others [4]
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