Letters in Organic Chemistry - Volume 22, Issue 6, 2025

Indole and its derivatives are important in both biology and chemistry due to their presence in many natural compounds and their role in various bodily functions. Indole is the core structure of several key molecules like tryptophan, serotonin, melatonin, and indole-3-acetic acid (IAA), which are involved in processes like cell signaling, growth regulation, and neurotransmission. Indole-based compounds in plants and animals serve as building blocks for essential molecules, such as alkaloids, proteins, and enzymes. For instance, in plants, indole derivatives like auxins help regulate growth, while in animals, they contribute to various physiological functions. Indole derivatives have been extensively researched for their potential as therapeutic agents, particularly in the pharmaceutical industry. These compounds exhibit a wide range of medicinal properties, including anticancer, antitubercular, antimalarial, and anti-HIV activities. Their anticancer potential is particularly notable, as they can target various biological pathways involved in cancer, such as inhibiting DNA topoisomerase, blocking histone deacetylase (HDAC), and disrupting tubulin polymerization. Modifying the indole structures by adding halogen atoms has increased their effectiveness, making them more potent than some standard chemotherapy drugs like cisplatin and gemcitabine. Indole-based compounds also show promise in targeting apoptosis (programmed cell death) and autophagy (cellular self-digestion), both of which are crucial in cancer treatment. By influencing these pathways, indole derivatives can promote the death of cancer cells and inhibit tumor growth, making them promising candidates for cancer therapy. The versatility and biological importance of the indole structure make it a valuable platform for drug development, with ongoing research aimed at understanding how these compounds can be used to treat cancer and other diseases.

Monkeypox is an emerging zoonotic disease caused by the monkeypox virus, a member of the Orthopoxvirus genus, characterized by symptoms, such as fever and lymphadenopathy, with distinctive skin rashes transmitted through direct contact with infected individuals or animals. Currently, there is no specific antiviral treatment approved for monkeypox; however, antiviral agents used for smallpox, such as tecovirimat and brincidofovir, have shown efficacy against monkeypox in laboratory studies. By analyzing recent outbreaks and response strategies, we aim to synthesize steroidal derivatives that may serve as potent therapeutic agents for this infectious disease. In the present research paper, we synthesized the methylprednisolone derivatives (1a-1d) with the help of Steglich esterification using a dehydrating agent N, Nꞌ-dicyclohexyldicarbodiimide (DCC) and N, Nꞌ-dimethyl-4-aminopyridine (DMAP) as a catalyst. The structures of all synthesized methylprednisolone derivatives were identified using advanced spectroscopic techniques, including ¹H NMR, ¹³C NMR, IR, UV-Vis, and ESI-MS. Experimental values correlated with theoretical predictions through DFT/B3LYP calculations. Hydrogen bonding and various interactions were thoroughly analyzed using Bader’s 'Atoms in Molecules' (AIM) theory. The HOMO-LUMO energy gap indicated a high level of chemical reactivity for the compounds, with Compound 1a exhibiting nonlinear optical (NLO) behavior due to a high first hyperpolarizability value of 9.06 × 10^–30 esu. Molecular docking studies of methylprednisolone derivatives 1a, 1b, 1c, and 1d against monkeypox protein (4QWO) revealed binding energies of -10.7 kcal/mol, -11.0 kcal/mol, -8.6 kcal/mol, and -9.3 kcal/mol, respectively. These results suggest that the methylprednisolone derivatives exhibit inhibitory activity against the monkeypox protein.

This research project focuses on the synthesis and characterization of a novel azo ligand, 4-CMBP, derived from 2-amino-6-methylbenzothiazole, and its complexes with Co(III) and Ni(II) ions. The study aims to investigate the structural and biological properties of the ligand and its complexes, with a particular emphasis on their potential applications in environmental and health sectors. The ligand and its complexes were characterized using techniques such as melting point measurements, nuclear magnetic resonance, mass spectrometry, Fourier-transform infrared spectroscopy, UV-Vis spectroscopy, elemental analysis, atomic absorption spectroscopy, molar conductivity, and magnetic susceptibility measurements. Biological activities were evaluated through the removal percentages of Co(III) and Ni(II) from eleven popular brands of lipsticks in the Iraqi market, antimicrobial screening against bacteria and fungi, in silico ADMET predictions, and anticancer activity tests in human liver cancer cell lines. Characterization confirmed the successful synthesis of the ligand and the formation of octahedral complexes with Co(III) and Ni(II) ions. The analysis revealed nickel concentrations ranging from 0.36 to 3.08 ppm, with varying safety implications. Antimicrobial screening showed promising activity, and in silico predictions indicated favorable oral bioavailability. The ligand and its complexes exhibited significant anticancer activity against liver cancer cell lines. The study successfully synthesized and characterized the azo ligand 4-CMBP and its metal complexes, highlighting their intriguing geometries and promising biological activities, with potential applications in environmental remediation, antimicrobial agents, and anticancer therapeutics.

The initial fundamental aspect examined in this study pertained to the chemical treatment of a silicon electrode in an acidic environment. The objective was to facilitate the deposition of organic or inorganic substances using electrochemical methods. Moreover, this study focused on investigating the nucleation process of poly(azacyclopenta-2,4-diene) on semiconductor substrates and exploring the incorporation of copper particles within the resulting film. The deposition of the polymer film onto the silicon electrode surface occurred through electrochemical oxidation of the monomer in a Na2SO4/H2O solution. The introduction of copper particles into the polymer film was achieved through electrochemical reduction in aqueous solutions, leading to the dispersion of metallic particles within the polymer matrix. Notably, the surface morphology of the poly(azacyclopenta-2,4-diene)-metal composite films exhibited a coarser and more compact structural appearance compared to pure poly(azacyclopenta-2,4-diene) films. To gain further insights into the surface characteristics of the poly(azacyclopenta-2,4-diene) films, EDX analysis confirmed the successful incorporation of copper into the composite films.

In this study, a domino multicomponent strategy was followed for the cyclo condensation reaction of aldehydes with β-ketoesters and hydroxylamine hydrochloride to produce a variety of 3,4-disubstituted isoxazol-5(4H)-ones using a novel Yttrium (III)-MMZ catalyst. Aprotic polar solvents and hard Lewis acid metal ions were found to greatly influence the reaction. In this study, the effect of the Y³⁺ in the MMZ framework and the nature of substrates and their positions in determining the yield of products were also described, along with a supporting mechanism. The structural morphology of Y³⁺-MMZ was characterized by the electron microscopic technique, and the loading level of Y³⁺ ions was determined by EDAX analysis. Most of the experiments did not require further purification by column chromatography. The present catalytic method offers several other advantages over the other reported methods, such as easy preparation, recyclization of the catalyst (up to 3 times), mild reaction conditions, shorter reaction time, and ease of work-up on recovering the products.