Browsing by Author "Kuran, Ebru Didem"

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Sub-Cytotoxic Mitochondrial Stress in Cardiomyocytes and Whole-Organism Toxicity in C. Elegans Induced by Molnupiravir
(SAGE Publications Inc, 2026) Gunaydin-Akyildiz, Aysenur; Keskin, Zehra; Ozhan, Gul; Kuran, Ebru Didem; Gulec, Meltem
Many antiviral agents are known to induce off-target mitochondrial toxicity due to the prokaryotic origin of mitochondria. Mitochondrial dysfunction is frequently linked to cardiotoxicity. We aimed to elucidate the mitochondrial toxicity profile of molnupiravir via focusing on mitochondrial dynamics, biogenesis, and oxidative stress in cardiac cells. Mitochondrial function was evaluated by luminometric measurement of ATP (adenosine triphosphate) content, and flow cytometric analysis of mitochondrial membrane potential, and mitochondrial mass. The expression levels of genes involved in mitochondrial fusion-fission were assessed by RT-PCR. In addition, molecular docking analysis was performed to evaluate the interaction between molnupiravir and the dynamin related-protein DRP1. Protein carbonylation was determined as an oxidative stress parameter. Toxicity evaluation was further investigated in Caenorhabditis elegans to support the in vitro findings at the organismal level. Molnupiravir exposure led to a significant dose-dependent reduction in intracellular ATP level and mitochondrial mass, accompanied by increased protein carbonylation. Mitochondrial membrane potential remained slightly increased. Alterations in the expression of genes regulating mitochondrial dynamics suggested an imbalance between fusion and fission processes, while mitochondrial biogenesis-related signaling was progressively suppressed. C. elegans exposed to higher concentrations of the drug (20-500 & micro;M) exhibited significant lifespan reduction at all doses. Molecular docking analysis demonstrated a moderate binding affinity of molnupiravir to DRP1, supporting a potential direct interaction with mitochondrial fission machinery. In conclusion, our results demonstrate that molnupiravir induces mitochondrial stress through oxidative damage, impaired biogenesis, and altered dynamics, emphasizing the need for careful evaluation of mitochondrial safety of molnupiravir in cardiac tissue.
Synthesis, Experimental and Quantum Mechanical Investigation of the Crystal Structures of Two Triazolyl-Indole Compounds, along with the Evaluation of Their Antioxidant Activity
(Elsevier, 2026) Pınar, Deniz; Kurt-Şirin, Özlem; Ulusoy-Güzeldemirci, Nuray; Dincel, Efe Doğukan; Karayel, Arzu; Kuran, Ebru Didem
In this study, two 1,2,4-triazolyl-indole compounds, 5-(1H-indol-3-yl)-4-propyl-2,4 dihydro-3H-1,2,4-triazole-3-thione (3a) and 5-(1H-indol-3-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (3b), were synthesized and the structures of these compounds were determined by X-ray diffraction method. These two compounds crystallize in the orthorhombic space groups, Pbca. The structures have been determined by direct methods and refined to R, 0.0459 (3a) and 0.0714 (3b). The molecular and crystal structures are stabilized by two intermolecular hydrogen bond for both molecules. The triazole parts of the molecules are almost perpendicular to propyl and butyl groups. NMR studies was also performed to enhance comprehension of the molecular structure of the compounds. The most stable states of the structures, as determined by both DFT analysis and experimental realizations (X-ray, NMR and FT-IR), are the thione form. Although the thione forms are thermodynamically more stable than the thiol forms (Delta H degrees approximate to-15 kcal/mol), they display higher chemical reactivity, as reflected by their smaller HOMO-LUMO energy gaps (Delta E = 4.374 eV for 3a and 4.377 eV for 3b). In addition, the antioxidant activities of both compounds were evaluated using ABTS, DPPH, and FRAP assays. Although both (3a) and (3b) exhibited measurable radical scavenging and reducing power, their antioxidant capacities were found to be lower than that of the reference compound quercetin.