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Thymidylate kinase (TMPK) of monkeypox virus (MPXV) has emerged as a promising target for potential therapeutics due to its significant role in pyrimidine metabolism. While smallpox drugs are advised for treating monkeypox, the European Medicine Agency has sanctioned Tecovirimat due to its potent nanomolar activity. Nonetheless, there is a need for monkeypox-specific therapeutic options. In this work, we employed docking-based virtual screening and molecular dynamics (MD) simulations to identify myxobacterial secondary metabolites as promising anti-viral natural compounds capable of inhibiting thymidylate kinase. The computational pharmacokinetics and manual curation of top-scoring compounds identified six lead compounds that were compared in terms of protein-ligand contacts and protein-essential dynamics. The study shows that among the six candidates, Aurachin A and the Soraphinol analogues such as Soraphinol A and Soraphinol C remain very stable compared to other compounds, enabling the active site integrity via a stable dynamics pattern. We also show that other compounds such as Phenoxan, Phenylnannolone C, and 8E-Aurafuron B remain unstable and have a negative impact on the active site integrity and may not be suitable binders for TMPK protein. Analyzing the Aurachin A and Soraphinol A binding, the established hydrogen bonds with Arg93 and the conserved hydrophobic interaction with Tyr101 are consistent with previous experimental interactions. Additionally, a deeper insight into the indole and the aromatic ring interaction through π–π stacking and π-cation interactions, as well as the background of Aurachin A and Soraphinol A as a bioactive compound, has significant implications not only for its potential as a promising drug but also for directing future drug discovery efforts targeting the TMPK protein. [ABSTRACT FROM AUTHOR]

The CuO–NiO bimetallic oxide nanoparticle (BMNP) was synthesized via a chemical route by varying the concentration of Ni2+. The prepared CuO–NiO BMNP was investigated using various analytical instruments. The direct bandgap of CuO–NiO BMNP was decreased from 5.45 to 4.85 eV with the increasing concentration of Ni2+. The XRD of the prepared sample confirmed the formation of a mixture of CuO–NiO BMNP. The crystallite size was calculated as 32 nm. The FT-IR spectrum showed the metal oxide stretching around 450–700 cm−1. The HR-TEM confirmed the BMNP formation with a particle size less than 20 nm. The catalytic activity of CuO–NiO BMNP was tested towards the reduction of a mixture of hazardous pollutants present in the effluent. The apparent rate constant (kapp) values were determined as 0.0217 × 10–2 s−1 for reduction of Cr(VI) and 0.0212 × 10–2 s−1 for reduction of Flur dye, respectively. The catalytic role of CuO–NiO BMNP was further confirmed by synthesizing the derivatives of indole and brilliant green (BG) dye. The experimental results were carefully analyzed and compared with the literature report. [ABSTRACT FROM AUTHOR]

A novel chemosensor exhibiting highly selective recognition of Cd over other metal ions with significant fluorescence quenching was designed and synthesized by a click reaction of dialkyne and indole azide precursors. The compound was identified by H NMR, C NMR, MS, and UV-vis spectroscopy. The fluorescence quenching phenomenon was observed with the addition of Cd . The reaction conditions, including the selectivity, the amount of Cd , reaction time, and temperature, were optimized in the article. The product exerted highly selective fluorescence change in the presence of Cd over other metal ions, such as Li, Na, K, Pb, Ni, Zn, Mn, Hg, Cr, Cu, and Fe. Under the optimal conditions, a linearly proportional relationship between fluorescence intensity and the concentration of Cd was revealed in the range from 0 to 7.226 × 10 M. The limit of detection was 2.69 μM. The results suggest that the substance synthesized with 2-methylindole is a novel and quick detector for Cd . [ABSTRACT FROM AUTHOR]

A series of chiral bis(oxazoline)thiophenes were used as chiral ligands in the Cu(II)-catalyzed asymmetric Friedel-Crafts alkylation of indole derivatives with nitroalkenes, and the effects of reaction conditions on the yield and enantioselectivity were investigated. The ligand 1c was identified as the best ligand of this family in the same reaction. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Synthesis and structure determination of 3-(naphth-1-ylmethyl)indole are reported. The molecular and crystal structures together with the molecular formula were determined by spectral and single crystal X-ray studies. X-ray crystallography revealed the presence of two conformers arising from the flipping of the naphthalene unit. The crystal of the compound belongs to the triclinic crystal system and space group $$P\bar 1$$ . Crystal data are as follows: a = 10.302(5) Å, b = 12.522(4) Å, c = 13.383(4) Å, α = 111.9(1)°, β = 116.86(6)°, γ = 71.65(5)°; V = 1726.429 Å3; Z = 4. The final R and Rw are R = 0.0744 (on observed F′s); R = 0.0924 (all F data), R w = 0.1757 (observed F 2) and R w = 0.1834 (all F 2 data). [ABSTRACT FROM AUTHOR]

As the main nitrogen source in Malassezia furfur, tryptophan induces the formation of fluorochromes and pigments, which make the yeast less sensitive to UV light. To detect a chemical UV filter, M. furfur (CBS 1878) was incubated at 30ºC for 14 days on a pigment-inducing medium and agar extracts were purified by column chromatography, preparative TLC and HPLC. Structural analysis of the pure metabolites was performed by mass spectroscopy and NMR. A yellow compound eluting from the column with 64% acetonitrile was found to be a potential UV filter because of its broad UV absorption (λmax 389, 315, 289, 212 nm). It was an indole derivative (C20H13N3O; pityriacitrin) which had recently been shown to be a potent UV filter in bacteria. Its UV protective properties were confirmed in a yeast model and also in humans. Pityriasis versicolor induced by Malassezia yeasts is characterized by depigmented skin areas showing reduced melanin synthesis but no increased UV sensitivity. This UV protection might be explained by the presence of pityriacitrin which is produced by M. furfur. [ABSTRACT FROM AUTHOR]

When administered i.p. from doses of 10 mg/kg, RU 23686 [5-methoxy 3-(4-piperidinyl) 1H-indole hydrochloride], a drug with relatively weak stimulant properties, induces contralateral (C) circling behaviour in rats with a unilateral electrolytic lesion in the striatum and a more complex effect with ipsilateral (1) and/or C circling in rats with a 6-hydroxydopamine (6-OHDA) lesion in the dopamine (DA) nigro-striatal tract. Interactions of RU 23686 with pharmacological agents have been studied in order to investigate the extent to which different neurotransmitters may be implicated in the circling behaviour induced by this compound. In striatal of 6-OHDA lesioned rats, α methyl p-tyrosine (αMT) did not modify C turns, while in the latter case only I turns were decreased. FLA 63, propranolol, and desipramine were also inactive in rats with a unilateral striatal lesion. Haloperidol reduced the effects of a 10 mg/kg dose of RU 23686 in striatal lesioned rats but was without effect against a dose of 20 mg/kg; in 6-OHDA lesioned rats, haloperidol blocked induced I turns but either did not affect or increased C turns. Phenoxybenzamine and p-chlorophenylalanine (PCPA), but not methysergide, p-chloroamphetamine (PCA), or fluoxetine, reduced the effect of RU 23686 in rats with a striatal lesion. In nigro-striatal lesioned rats, PCPA exhibited a differing effect according to the predominance of I or C turns: in rats with a mainly C response, C turns were decreased and I turns preserved, whereas in rats with a majority of I responses, these were depressed. In both types of lesions, animals reserpinized 48 h before RU 23686 exhibited an increase in their C circling, even in 6-OHDA lesioned animals where I turns predominated. In both rotational models, apomorphine-induced circling was potentiated by RU 23686. It is concluded that I circling, which is blocked by haloperidol and αMT, could be related to a presynaptic action causing DA release. On the other hand, C turns do not depend on apomorphine-sensitive DA receptors in the striatum. A minor or indirect role of 5-hydroxytryptamine (5-HT) containing areas is suggested from the response to PCPA and the lack of effect of other drugs interfering with 5-HT. Results obtained from interactions with phenoxybenzamine, caffeine, and reserpine and the bimodal response to RU 23686 observed in 6-OHDA lesioned rats could indicate an interference with adrenergic processes. [ABSTRACT FROM AUTHOR]