Structural Analogy — Direct Similarity Versus Topographical Complementarity

Kafarski, Paweł; Lipok, Magdalena

doi:10.5772/59401

Cited by 3 publications

(2 citation statements)

References 76 publications

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“…Substructure similarity analysis of drugs has been used successfully in the past for selection and ranking of hits after high throughput screening assays (Martin et al ., 2002). Additionally, it can be the groundwork of structural analogy studies, for the design and the development of new drugs (Kafarski and Lipok, 2015).…”

Section: Resultsmentioning

confidence: 99%

Rescue of the increased susceptibility to Mild Chronic Oxidative Stress of iNeurons carrying the MAPT Chromosome 17q21.3 H1/H1 risk allele by FDA-approved compounds

Sadikoglou

Domingo‐Fernándéz

Savytska

et al. 2022

Preprint

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The microtubule associated protein tau (MAPT) chromosome 17q21.31 locus lies within a region of high linkage disequilibrium (LD) conferring two extended haplotypes commonly referred to as H1 and H2. The major haplotype, H1 has been genetically associated with an increased risk for multiple neurodegenerative disorders, including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), APOE epsilon4-negative Alzheimer`s disease (AD) and Parkinson`s disease (PD). The mechanism causing this increased risk is largely unknown. Here, we investigated the role of Mild Chronic Oxidative Stress (MCOS) in neurogenin 2 (NGN2) induced neurons (iNeurons) derived from iPS (induced pluripotent stem cells) from carriers of both haplotypes. We identified that iNeurons of the H1 homozygous haplotype showed an increased susceptibility to MCOS compared to homozygous H2 carriers, leading to cell death through ferroptosis. We performed a cellular screen in H1 iNeurons using a FDA-approved Drug Library and identified candidate molecules that rescued the increased susceptibility to MCOS and prevented ferroptosis in H1 iNeurons.

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Section: Resultsmentioning

confidence: 99%

Rescue of the increased susceptibility to Mild Chronic Oxidative Stress of iNeurons carrying the MAPT Chromosome 17q21.3 H1/H1 risk allele by FDA-approved compounds

Sadikoglou

Domingo‐Fernándéz

Savytska

et al. 2022

Preprint

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“…Numerous dyes and their derivatives have found medical applications as diagnostic and therapeutic agents, and new dyes have been developed from the research on antiparasite diseases [4,5]. Thus, the azo dye chrysoidin led to the antibacterial p-sulfamido derivative (prontosil), some bisazo trypanocide dyes (Trypan red and blue) led to the discovery of arsenicals and aryl-urea derivatives (suramin) [6][7][8], etc. Other examples are antimalarial quinacrine and chloroquine, antibacterial acridines and triarylmethanes, antiseptic xanthenes, tumor-markering and psychotropic phenothiazines, antitumoral and antiviral photosensitizing (photodynamic) agents, antitrypanosomal aromatic diamidine fluorochromes, etc.…”

Section: Introductionmentioning

confidence: 99%

Melanin-Binding Colorants: Updating Molecular Modeling, Staining and Labeling Mechanisms, and Biomedical Perspectives

2022

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Melanin and melanoma tumors are two fields of increasing interest in biomedical research. Melanins are ubiquitous biopigments with adaptive value and multiple functions, and occur in the malignant melanoma. Although several chemical structures have been proposed for eumelanin, molecular modeling and orbitals indicate that a planar or spiral benzoquinone-porphycene polymer would be the model that better explains the broad-band light and ultrasound absorption, electric conductivity, and graphite-like organization shown by X-ray crystallography and electron microscopy. Lysosomes and melanosomes are selectively labeled by vital probes, and melanin also binds to metal cations, colorants, and drugs, with important consequences in pharmacology, pathology, and melanoma therapy. In addition to traditional and recent oncologic treatments, photodynamic, photothermal, and ultrasound protocols represent novel modalities for melanoma therapy. Since eumelanin is practically the ideal photothermal and ultrasound sensitizer, the vibrational decay from photo-excited electrons after NIR irradiation, or the electrochemical production of ROS and radicals after ultrasound absorption, induce an efficient heating or oxidative response, resulting in the damage and death of tumor cells. This allows repetitive treatments due to the remaining melanin contained in tumoral melanophages. Given that evolution and prognosis of the advanced melanoma is still a concern, new biophysical procedures based on melanin properties can now be developed and applied.

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Computational identification of potential tau tubulin kinase 1 (TTBK1) inhibitors: a structural analog approach

Purushothaman,

Sivasankar,

Krishnamoorthy

et al. 2024

In Silico Pharmacol.

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Structural Analogy — Direct Similarity Versus Topographical Complementarity

Cited by 3 publications

References 76 publications

Rescue of the increased susceptibility to Mild Chronic Oxidative Stress of iNeurons carrying the MAPT Chromosome 17q21.3 H1/H1 risk allele by FDA-approved compounds

Rescue of the increased susceptibility to Mild Chronic Oxidative Stress of iNeurons carrying the MAPT Chromosome 17q21.3 H1/H1 risk allele by FDA-approved compounds

Melanin-Binding Colorants: Updating Molecular Modeling, Staining and Labeling Mechanisms, and Biomedical Perspectives

Computational identification of potential tau tubulin kinase 1 (TTBK1) inhibitors: a structural analog approach

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