Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

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 treatmen

Differential Proliferation Effect of the Newly Synthesized Valine, Tyrosine and Tryptophan–Naphthoquinones in Immortal and Tumorigenic Cervical Cell Lines

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 treatmen

Synthesis of Hybrid Fluoroquinolone-Boron Complexes and Their Evaluation in Cervical Cancer Cell Lines

Quinolones are a family of antimicrobial agents that have been used in antibacterial and anticancer chemotherapy. Fluoroquinolone targets DNA gyrase and topoisomerase IV enzymes affecting several cellular processes, like cell death and proliferation; the best way to act is in the form of carboxylic acid or, recently, as quinolone-metal complex. In this work, the use of boron is shown as an alternative of metal to form a complex by incorporating to fluoroquinolone as an electron withdrawing substituent to activate the C-7 position chemoselectively for the production of new fluoroquinolone hybrids and test their effects on cell proliferation. Fluoroquinolone-boron complexes were synthesized according to the Gould–Jacobs cyclization method, and five hybrid fluoroquinolone-boron compounds were obtained by SNAr reaction, yielding 31 to 46%, at 80°C, and in 10 to 25 hours of reaction. The effect of the five fluoroquinolone-boron hybrids was evaluated in cervical cancer cell lines by cell proliferation assay. 7-hydantoin-fluoroquinolone-boron and 7-dihydropyridine-fluoroquinolone-boron complexes showed the strongest effect according to dose-response assay, respectively. The fluoroquinolone-boron hybrid complex showed proliferation inhibition in SiHa and CasKi cells, opening the possibility to use them as potential agents for the treatment of cancer

Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

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