RESUMEN
Dimethylamine (DMA) derivatives represent a promising class of compounds with significant potential in the field of medicinal chemistry. DMA derivatives exhibit a diverse range of pharmacological activities, including antimicrobial, antihistaminic, anticancer, and analgesic properties. Their unique chemical structure allows for the modulation of various biological targets, making them valuable candidates for the treatment of numerous diseases. Synthetic strategies for the preparation of DMA derivatives vary depending on the desired biological activity and target molecule. Common synthetic routes involve the modification of the DMA scaffold through functional group manipulation, scaffold hopping, or combinatorial chemistry approaches. Therapeutically, DMA derivatives have shown promise in the treatment of infectious diseases, especially bacterial infections. Additionally, by focusing on particular biochemical pathways involved in tumor growth and metastasis, DMA-based drugs have shown anticancer activity. In addition to their direct pharmacological effects, DMA derivatives can serve as valuable tools in drug delivery systems, prodrug design, and molecular imaging techniques, enhancing their utility in medicinal chemistry research. Overall, DMA derivatives represent a versatile class of compounds with immense potential in medicinal chemistry. Further research and development efforts are warranted to explore their full therapeutic capabilities and optimize their clinical utility in the treatment of various diseases. This article outlines the pharmacological properties, synthetic strategies, and therapeutic applications of DMA derivatives of FDA approved drugs, highlighting their importance in drug discovery and development.
RESUMEN
Eighteen compounds derived from two sub-series, (HC1-HC9) and (HF1-HF9), were synthesized and evaluated for their inhibitory activities against monoamine oxidase (MAO). HC (chalcone) series showed higher inhibitory activity against MAO-B than against MAO-A, whereas the HF (chromone) series showed reversed inhibitory activity. Compound HC4 most potently inhibited MAO-B with an IC50 value of 0.040 µM, followed by HC3 (IC50 = 0.049 µM), while compound HF4 most potently inhibited MAO-A (IC50 = 0.046 µM), followed by HF2 (IC50 = 0.075 µM). The selectivity index (SI) values of HC4 and HF4 were 50.40 and 0.59, respectively. Structurally, HC4 (4-OC2H5 in B-ring) showed higher MAO-B inhibition than other derivatives, suggesting that the -OC2H5 substitution of the 4-position in the B-ring contributes to the increase of MAO-B inhibition, especially -OC2H5 (HC4) > -OCH3 (HC3) > -F (HC7) > -CH3 (HC2) > -Br (HC8) > -H (HC1) in order. In MAO-A inhibition, the substituent 4-OC2H5 in the B-ring of HF4 contributed to an increase in inhibitory activity, followed by -CH3 (HF2), -F (HF7), -Br (HF8), -OCH3 (HF3), and-H (HF1). In the enzyme kinetics and reversibility study, the Ki value of HC4 for MAO-B was 0.035 ± 0.005 µM, and that of HF4 for MAO-A was 0.035 ± 0.005 µM, and both were reversible competitive inhibitors. We confirmed that HC4 and HF4 significantly ameliorated rotenone-induced neurotoxicity, as evidenced by the reactive oxygen species and superoxide dismutase assays. This study also supports the significant effect of HC4 and HF4 on mitochondrial membrane potential in rotenone-induced toxicity. A lead molecule was used for molecular docking and dynamic simulation studies. These results show that HC4 is a potent selective MAO-B inhibitor and HF4 is a potent MAO-A inhibitor, suggesting that both compounds can be used as treatment agents for neurological disorders.