Drugs and Drug Candidates

In the publication [...]

Background: Tuberculosis (TB) remains a critical global health concern, exacerbated by the emergence of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis. In the search for novel therapeutic agents, naphthoquinones have garnered interest due to their diverse mechanisms of action and potent antimycobacterial activity. In this study, we report the design, synthesis, and biological evaluation of a novel series of eleven naphthoquinone-based derivatives (compounds 22–32), developed through a molecular hybridization strategy targeting shikimate kinase (Mtb-SK) an essential enzyme present exclusively in M. tuberculosis. Methods: The compounds were synthesized via a straightforward and efficient synthetic route, and preliminary screening identified five molecules with significant anti-TB activity. Notably, compound 26, 4-(4-ethoxyphenyl) amino) Naphthalene-1,2-dione, exhibited a minimum inhibitory concentration (MIC) of 21.33 µM, comparable to ethambutol and substantially more potent than pyrazinamide. Results: Molecular docking studies indicated that all active compounds interact favorably within the shikimate binding pocket of Mtb-SK, following the proposed mechanism of action. Additionally, ongoing cytotoxicity assays in HepG2 cells aim to assess the selectivity of these derivatives. Conclusions: These findings support the potential of this new class of naphthoquinones as promising scaffolds for the development of anti-TB agents, contributing to the growing body of research focused on new chemotherapeutic options against tuberculosis.

Background/Objectives: Colon cancer is the third most common type of cancer in the world, characterized by a high risk of metastasis, resistance to various drugs, and late diagnosis. In addition, the drugs used for treatment are associated with serious neurological damage, causing acute and chronic pain and compromising the patient’s quality of life. Meanwhile, lectins are proteins capable of exerting cytotoxic action on cells from various tumors in a selective manner, without exerting significant toxicity on healthy cells. Despite this, studies on the potential of lectins obtained from microalgae are still scarce in the literature. In this sense, the objective of this study was to evaluate the antitumor activity of lectin isolated from the microalgae Chlorella vulgaris (CvL) on colorectal cancer cells, HT-29. Methods: The purified lectin was tested for cytotoxicity using MTT colorimetric methods, in addition to clonogenicity, cell cycle, apoptosis, and necrosis tests, analyzed by flow cytometry. Results: The assays demonstrated that the lectin was able to induce cell death in the HT-29 tumor line by approximately 83.75% with an IC₅₀ value of 21.5 µg/mL⁻¹, reduced colony formation by more than 90%, was able to regulate the cell cycle by apoptosis, and did not present significant necrosis. These results show that microalgae lectins have the potential to be exploited in the control of neoplastic cells.