Desenvolvimento de metodologias verdes e sustentáveis para a obtenção de agentes quimioterápicos a partir de resíduos de processamento de manga (Mangifera indica L.)

Abstract

Brazilian agro-industrial production generates alarming amounts of waste. In recent years, mango production has grown significantly, with the state of São Paulo among the largest producers, discarding tons of waste annually. These residues are rich in high-value bioactive compounds, and studies have investigated their antitumor potential due to the presence of secondary metabolites. Given the projected increase in cancer cases, exploring mango waste as a source of new anticancer drugs is a promising approach. Practices aligned with sustainable development should be adopted, with emphasis on using Green and Sustainable Chemistry principles, promoting the creation of products and processes that prevent the generation and use of environmentally harmful substances. Concepts such as biorefinery and circular economy are applicable in this context, utilizing biomass as a raw material to obtain new products. This study aimed to develop green and sustainable analytical methods for obtaining a chemotherapeutic agent through the extraction of secondary metabolites from mango waste. Bioassay-guided experiments on tumor cell lines, combined with spectrometric analyses using test extracts and their fractions, allowed the annotation of the target analytes: gallic acid and methyl gallate. Using chemometric techniques, two extraction methods were evaluated and optimized: homogenization-assisted extraction and microwave-assisted extraction, employing only green solvents such as water and ethanol, and considering the influence of the variables in the extraction. The extracts were analyzed by liquid chromatography coupled with mass spectrometry. The analytes were quantified based on analytical curves, demonstrating selectivity, linearity (R² > 0.999), detection and quantification limits suitable for the linear range, as well as precision (< 2%), accuracy (> 96%), and recovery (> 94%). Among the evaluated variables, ethanol composition (40% v.v⁻¹) in water and the number of extractions (1×) were the most relevant for the optimized extract obtained by homogenization. For the optimized extract obtained by microwave-assisted extraction, ethanol composition (80% v.v⁻¹) in water and temperature (70°C) were the most critical factors. The antitumor properties of test extracts, optimized extracts, and analytical standards of gallic acid and methyl gallate were evaluated in lung and ovarian cancer cell lines, as well as in non-tumor lung cells. The optimized extracts presented lower IC50 values compared to the test extracts, demonstrating greater selectivity for tumor cells. The optimized extract obtained by microwave-assisted extraction was the most promising, with IC50 values of 6.09 and 0.21 μg.mL⁻¹ for lung and ovarian tumor cells, respectively. The optimized extracts showed IC50 values comparable to the drugs cisplatin and doxorubicin, with significantly higher selectivity for tumor cells. A comparison between the extracts and analytical standards revealed a strong synergistic interaction among the matrix compounds. Morphological and clonogenic assays demonstrated that the optimized extracts exhibit cytostatic and cytotoxic profiles, indicating cell death. The results highlight the potential for reusing mango waste to obtain antitumor agents using green analytical methodologies.