Monoacylglycerol lipase (MAGL) is an enzyme belonging to the endocannabinoid system that mainly metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG). Numerous studies have shown the involvement of this enzyme in various pathological conditions such as pain, cancer progression, Parkinson's and Alzheimer's disease, thus encouraging the development of new MAGL modulators. In this context, we developed new diphenylsulfide-benzoylpiperidine derivatives characterized by a high enzymatic MAGL inhibition activity in the low nanomolar range, a reversible mechanism of action and selectivity. The three most active compounds (15–17) induced an appreciable inhibition of cell viability in a panel of nine cancer cell lines, with IC₅₀ values ranging between 0.32 and 10 μM, thus highlighting their potential as novel anticancer agents.

单酰基甘油脂肪酶 (MAGL) 是一种属于内源性大麻素系统的酶，主要代谢内源性大麻素 2-花生四烯酸甘油 (2-AG)。大量研究表明，这种酶参与各种病理状况，如疼痛、癌症进展、帕金森氏病和阿尔茨海默氏病，从而促进了新 MAGL 调节剂的开发。在这种情况下，我们开发了新的二苯硫醚-苯甲酰基哌啶衍生物，其特征是在低纳摩尔范围内具有高酶促 MAGL 抑制活性，具有可逆的作用机制和选择性。三种最活跃的化合物 ( 15 – 17 ) 在一组九种癌细胞系中诱导了细胞活力的明显抑制，IC ₅₀ 值范围在 0.32 到 10 μM 之间，从而突出了它们作为新型抗癌剂的潜力。