Oral squamous cell carcinoma (OSCC) is a global public health problem with high incidence and mortality. The chemotherapeutic agents used in the clinic, alone or in combination, usually lead to important side effects. Thus, the discovery and development of new antineoplastic drugs are essential to improve disease prognosis and reduce toxicity. In the present study, acridine-core naphthoquinone compounds were synthesized and evaluated for their antitumor activity in OSCC cells. The mechanism of action, pharmacokinetics, and toxicity parameters of the most promising compound was further analyzed using in silico, in vitro, and in vivo methods. Among the derivatives, compound 4e was highly cytotoxic (29.99 µM) and selective (SI 2.9) at levels comparable and generally superior to chemotherapeutic controls. Besides, compound 4e proved to be non-hemolytic, stable, and well tolerated in animals at all doses tested. Mechanistically, compound 4e promoted cell death by apoptosis in the OSCC cell, and molecular docking studies suggested this compound possibly targets enzymes important for tumor progression, such as RSK2, PKM2, and topoisomerase IIα. Importantly, compound 4e presented a pharmacological profile within desirable parameters for drug development, showing promise for future preclinical trials.
Abstract:With the advent of green chemistry, the industry becomes more and more attempting to reverse the pollution releasing state of its process, combining progress with the development of technologies and processes less harmful to the planet. The synthetic chemists are improving the methodologies of synthesis in order to generate fewer residues. The oxidation of alcohols, one of the most important chemical transformations in the industry, already presents various techniques according to the philosophy of green chemistry. This article will show some of the new techniques used for the oxidation of alcohols, including a brief review of the main conventional methods.Keywords: Oxidation; alcohol; green chemistry; sustainable chemistry; clean chemistry.
ResumoCom o surgimento da química verde, as indústrias tentam cada vez mais reverter o impacto da poluição relacionada a seus processos, aliando o progresso com tecnologias e procedimentos menos danosos ao planeta. Os químicos sintéticos estão aprimorando as metodologias de síntese para gerar um menor número de resíduos. A oxidação de alcoóis, uma das principais transformações químicas na indústria, já apresenta técnicas variadas que atendem a filosofia da química verde. Neste artigo serão mostradas alguns novos métodos utilizados para a oxidação de alcoóis, além de uma pequena revisão sobre os principais métodos convencionais.
Palavras-chave:Oxidação; álcool; química verde; química sustentável; química limpa.
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