ABSTRACT
We analyzed here the in silico biological activities of caffeine, (+)-catechin, and theobromine. For this, the PubChem database of the NIH (National Institutes of Health) was used to obtain the SMILE canonical form of the bioactive molecules, and the free software PASS Online (Prediction of Activity Spectra for Substances) from the Way2Drug portal. Also, we conducted an in vitro experiment using a chronic myeloid leukemia (CML) cell line (K562) to confirm some results found in in silico investigation. These cells were exposed to different concentrations of caffeine, (+)-catechin, and theobromine for 72 h. The results found in this in silico study suggested that caffeine, (+)-catechin, and theobromine showed excellent biological properties, such as antioxidant, anti-inflammatory, and anticarcinogenic, as well as protection against cardiovascular, diabetes, neurological, allergic, respiratory, and other therapeutic activities. These findings can be elucidated through the modulation exerted by these bioactive molecules in many biochemical pathways involved in organism homeostasis, such as free radical scavenger action, oxidoreductase inhibitor, membrane permeability inhibitor, and lipid peroxidase inhibitor. In addition, we have found here that caffeine, (+)-catechin, and theobromine have a remarkable anti-inflammatory activity which plays an important role in the therapeutic approach of COVID-19. Moreover, our in vitro findings confirmed the in silico results regarding anticancer activity since these molecules reduce cell proliferation at all tested concentrations. Therefore, since these molecules exhibit important medicinal activities, further investigations should be conducted to reveal new therapies to improve the treatments and prevention of numerous disorders and, consequently, promote human health.
ABSTRACT
Renal neoplasms are highlighted as one of the 10 most common types of cancer. Renal cell carcinoma (RCC) is the most common type of renal cancer, considered the seventh most common type of cancer in the Western world. The most frequently altered genes described as altered are VHL, PBRM1, SETD2, KDM5C, PTEN, BAP1, mTOR, TP53, TCEB1 (ELOC), SMARCA4, ARID1A, and PIK3CA. RCC therapies can be classified in three groups: monoclonal antibodies, tyrosine kinase inhibitors, and mTOR inhibitors. Besides, there are targeted agents to treat RCC. However, frequently patients present side effects and resistance. Even though many multidrug resistance mechanisms already have been reported to RCC, studies focused on revealing new biomarkers as well as more effective antitumor therapies with no or low side effects are very important. Some studies reported that natural products, such as honey, epigallocatechin-3-gallate (EGCG), curcumin, resveratrol, and englerin A showed antitumor activity against RCC. Moreover, nanoscience is another strategy to improve RCC treatment and reduce the side effects due to the improvement in pharmacokinetics and reduction of toxicities of chemotherapies. Taking this into account, we conducted a systemic review of recent research findings on RCC hallmarks, drug resistance, and adjuvant therapies. In conclusion, a range of studies reported that RCC is characterized by high incidence and increased mortality rates because of the development of resistance to standard therapies. Given the importance of improving RCC treatment and reducing adverse effects, nanoscience and natural products can be included in therapeutic strategies.
