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The syntheses of novel spirobenzazepinoindole derivatives has been achieved through a highly efficient and synthetic route. The approach involves a two-step reaction, utilizing indole derivatives, 2-amino benzyl alcohol, and ninhydrin as key starting materials under mild reaction conditions. The reaction proceeds via a sequential cascade process involving cyclization, condensation and spiro-annulation, leading to the formation of the spirobenzazepinoindole core structure in good to excellent yields. The method offers broad substrate scope, high atom economy, and operational simplicity. The synthesized spirobenzazepinoindoles were fully characterized by spectroscopic techniques, including NMR ( 1 H & 13 C), IR and mass spectrometry. The methodology provides a valuable tool for the rapid generation of structurally complex spirobenzazepinoindoles, which could serve as scaffolds for the development of new therapeutic agents., (© 2024 Wiley-VCH GmbH.)

The indole motif plays a significant role in the quest for innovative drugs. As proposed, novel N‐substituted indole derivatives were synthesized, and their efficacy against bacteria and fungi was evaluated in vitro. The synthesis of these compounds was confirmed using easily accessible building blocks, and their structural formulas were supported by corrected analytical and spectroscopic analyses. Fresh strains of Candida albicans, Escherichia coli, and Pseudomonas aeruginosa, as well as Bacillus subtilis and Staphylococcus aureus, were utilized to assess the antibacterial and antifungal activities. Notably, the derivatives 1‐(phenyl (piperidine‐1‐yl) methyl)‐1H‐indole and 4‐(1H‐indol‐1‐yl) (phenyl) morpholine have strong antifungal effects on Candida albicans that are equivalent to those of the widely used drug fluconazole. [ABSTRACT FROM AUTHOR]

In this work, we synthesized new 5, 6, 7, 8-tetrahydroisoquinolines and 6, 7, 8, 9-tetrahydrothieno[2, 3-c]isoquinolines derivatives, and the structures of these new compounds were confirmed with different spectroscopic techniques. Furthermore, the anticancer activities of these compounds were assessed against eight tumor cell lines and one normal human skin fibroblast cell line (HSF). Subsequently, IC 50 values of the synthesized compounds were determined for two specific cancer cell lines. Compound 3 exhibited the most potent antiproliferative activity against the HEPG2 cell line, whereas compound 9c demonstrated superior efficacy against the HCT116 cell line. Moreover, the mechanism of action for compound 3 on HEPG2 cells using flow cytometry and Annexin V-FITC apoptosis analysis was studied. Compound 3 caused cell cycle arrest at the G2/M with a 50-fold increase in apoptosis of the HEPG2 cell line. Finally, a molecular docking study was conducted to assess the inhibitory potential of compounds 3 and 7 against the RET enzyme. Results indicated that compounds 3 and 7 bind to the RET enzyme with binding energies of -5.2 and -5.6 kcal/mol, respectively. Although these values suggest inhibitory activity, they are less potent than the standard inhibitor, alectinib, which exhibits a binding energy of -7.2 kcal/mol., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Melatonin (MLT) is a natural indolic hormone with well documented antioxidant properties, but it can also modulate the estrogen signaling pathway by inhibiting the aromatase enzyme and estrogen receptor modulating activity. This dual activity raises concerns about potential endocrine-related adverse effects when using MLT and its analogues as therapeutic agents in the prevention and treatment of oxidative stress related diseases. In this study, 34 novel 5-fluoroindole derivatives of MLT were synthesized and evaluated for their antioxidant, estrogen receptor modulatory, and aromatase inhibitory activities.Three compounds (4c, 5c, and 6c) demonstrated significant antioxidant activity, with compound 4c showing the highest efficacy in reducing intracellular reactive oxygen species (ROS) by 65 % in CHO-K1 cells and displaying DPPH radical scavenging comparable to the standard antioxidant, BHT. However, these same compounds also exhibited antiestrogenic effects in the E-Screen assay, with IC 50 values of 3.36×10 -5  M, 1.31×10 -7  M, and 1.9×10 -7  M, respectively, and inhibited aromatase activity by up to 29 % in a direct enzymatic assay. These findings indicate that, while the compounds have potent antioxidant properties, their significant antiestrogenic and aromatase inhibitory activities may pose risks for unintended endocrine related effects. Further studies are needed to better understand the implications of these activities in vivo and to balance the benefits and risks of such compounds in therapeutic applications., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)