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Go to Editorial ManagerBackground A major limitation is the low selectivity of conventional chemotherapeutic agents, which results in severe toxicity on non-malignant tissues. Scaffolds based on indole have recently been identified as interesting new anticancer candidates but selective cytotoxicity continues to be a key target. Objective The goal of this study was to determine the cytotoxic and specific anticancer effects of a novel 5-bromo-indole-derived carbothioamide (BTIC) on several malignant and non-cancerous cell lines. Methods After a 48-hour treatment, BTIC's antiproliferative effectiveness against human breast cancer (MCF-7), lung cancer (A549), & normal endothelium (HUVEC) cell lines was evaluated using the MTT assay. Data shown as dose-response curves were subjected to nonlinear regression analysis to determine IC50 values. Preferential cytotoxicity was evaluated using the selectivity index (SI). Results In every cell line examined, BTIC had a cytotoxic impact; furthermore, this toxicity was concentration-dependent. This compound exhibited the most powerful activity against A549 cells (IC50 = 3.5 µg/mL), followed by MCF-7 cells IC50 (5.4 µg/mL), and significant cytotoxicity was recorded in HUVEC cells (IC50 = 10.4 µg/mL). A selective cytotoxicity on cancer cells was suggested by these reported SI values (2.97 and 1.93 for A549 and MCF-7, respectively). Conclusion BTIC was also a lead chemical with potent anticancer action against lung cancer cells in vitro, which exhibited high specificity. Therapeutic translation requires additional mechanistic and in vivo studies.
Objective: Histone deacetylase-2 (HDAC-2) has emerged as an important molecular target in cancer therapy because of its role in gene silencing, regulation of the cell cycle, and resistance to apoptosis in several cancer types. In the present study, a series of novel 4-aminoantipyrine-based derivatives incorporating semicarbazide, thiosemicarbazide, and hydroxylamine pharmacophoric groups were rationally designed and evaluated for their potential HDAC-2 inhibitory activity using in silico approaches. Methods:. The binding affinity of the newly designed compounds toward the HDAC-2 enzyme and their interactions within the catalytic pocket were investigated using molecular docking analysis. The three-dimensional structure of HDAC-2 (PDB ID: 4LXZ) was obtained from the RCSB Protein Data Bank and prepared for docking studies. Results: Docking indicated that ligand stability within the enzyme active site was mainly achieved through coordination with the catalytic zinc ion, in addition to hydrogen bonding and hydrophobic interactions with essential amino acid residues located in the HDAC-2 catalytic domain. The reference inhibitor vorinostat (SAHA) was used as a standard compound and produced a docking score of −5.445 kcal/mol. Among the designed compounds, Compound Ia exhibited the most favorable binding energy with a calculated ΔG of −9.711 kcal/mol. In addition, Compound IIe and Compound Ib demonstrated promising docking scores of −8.285 and −8.147 kcal/mol, respectively. Conclusions: Pharmacokinetic properties were predicted using the QikProp module, revealing that most designed compounds exhibited acceptable drug-likeness according to Lipinski’s Rule of Five. These computational findings suggest that the designed derivatives may represent promising candidates as HDAC-2 inhibitors with potential anticancer activity.
Schiff bases have been a very important category of chemical molecules in medicine and pharmacology over the last several decades. Their structure contains an azomethine functional group (-C=N-).This group is typically formed by the condensation of primary amines with aldehydes or ketones. Schiff bases are relatively easy to synthesize, and their structural versatility allows modification for diverse biological applications. From a medicinal standpoint, Schiff bases have demonstrated a wide range of biological activities, including antimicrobial, anticancer, anti-inflammatory, antioxidant, and antiviral effects.Multiple studies suggest that even small alterations in chemical structure, such changes in substituent characteristics or the introduction of heterocyclic groups, may substantially affect biological efficacy. Schiff bases are also recognized for their ability to coordinate with metal ions, which has led to the development of numerous metal complexes with new or improved pharmacological characteristics.The medicinal significance of Schiff bases is further supported by their proposed mechanisms of action, including enzyme inhibition, interaction with microbial cell membranes, DNA binding, and modulation of oxidative stress pathways.These characteristics make Schiff bases attractive frameworks for the development of novel therapeutic agents.This review aims to highlight the pharmaceutical importance of Schiff bases by focusing on their chemical characteristics and key antibacterial, antifungal, antiviral, and anticancer activities, while also discussing their potential applications in drug discovery and development.
Objective Angiogenesis is an essential process in tumor growth and progression, and thus it represents a promising therapeutic target. Lawsonia inermis (henna) is a widely-used traditional medicine with different biological applications, and its bioactive components, especially lawsone, showed anticancer activity. The objective of this research was to measure the anti-angiogenic and antioxidant properties of Lawsonia inermis leaf ethanolic extract in ex vivo and in vivo systems. Methods Soxhlet was used to prepare the ethanolic extract of the Lawsonia inermis leaf. The ex vivo rat aorta ring assay was used to test the anti-angiogenic activity at the concentrations of 100, 50, 25, 12.5, and 6.25 µg/mL. The in vivo chick chorioallantoic membrane (CAM) assay was employed to confirm the anti-angiogenic effect at a concentration of 10 mg/mL. DPPH radical scavenging assay was used to determine the antioxidant activity with a concentration range of 3.125 to 100 µg/mL. Results The ethanolic extract demonstrated high anti-angiogenic activity in the rat aorta ring with 65.82% inhibition at 100 µg/mL and dose-dependent inhibition with an IC 50 of 54.2 µg/mL. In the CAM assay, acetylsalicylic acid (positive control) resulted in complete suppression of vascularization, validating the assay system. The extract exhibited a concentration-dependent radical scavenging ability of DPPH radical with an IC 50 value of 0.05 µg/mL. Conclusions Lawsonia inermis ethanolic extract has strong anti-angiogenic and antioxidant properties, which implies its possible application as a treatment of angiogenesis-related disorders, such as cancer. The anti-angiogenic effect was confirmed in both ex vivo and in vivo models.