2-Meth­oxy-3-[(3,4,5-trimethoxy­anilino)methyl­idene]-3,4-dihydro-2H-1-benzopyran-4-one

The title mol­ecule, C20H21NO6, adopts a keto–amine tautomeric form. An intra­molecular N—H⋯O hydrogen bond, classified as a resonanse-assisted hydrogen bond, influences the mol­ecular conformation; the two benzene rings form a dihedral angle of 24.6 (1)°. In the crystal structure, weak inter­molecular C—H⋯O hydrogen bonds link mol­ecules into chains propagating along [001]

Crystal structures of (E)-3-(4-hy­dr­oxy­benzyl­­idene)chroman-4-one and (E)-3-(3-hy­dr­oxy­benzyl­­idene)-2-phenyl­chroman-4-one

The synthesis and crystal structures of (E)-3-(4-hy­droxy­benzyl­idene)chroman-4-one, C16H12O3, I, and (E)-3-(3-hy­droxy­benzyl­idene)-2-phenyl­chroman-4-one, C22H16O3, II, are reported. These compounds are of inter­est with respect to biological activity. Both structures display inter­molecular C—H⋯O and O—H⋯O hydrogen bonding, forming layers in the crystal lattice. The crystal structure of compound I is consolidated by π–π inter­actions. The lipophilicity (logP) was determined as it is one of the parameters qualifying compounds as potential drugs. The logP value for compound I is associated with a larger contribution of C⋯H inter­action in the Hirshfeld surface.Funding for this research was provided by: Uniwesytet Łódzki, Uniwersytet Medyczny w Łodzi (grant No. SGB_148_Suchojad_Kamil to K. Suchojad; grant No. 502-03/3-066-02/502-34-118 to A. Adamus-Grabicka, E. Budzisz)

New look at the role of progerin in skin aging

Current literature data indicate that progerin, which is a mutant of lamin A, may be one of several previously known physiological biomarkers of the aging process which begins at the age of 30. Lamins belong to the family of intermediate filaments type V and are an important component of the nuclear envelope (NE). The physiological processes of an alternative splicing of LMNA (lamin A/C) gene and posttranslational processing result in the formation of different variants of this gene. Prelamin A is generated in cytosol and modified by respective enzymes. In the final step, 15-aa peptide is released at the C-terminus, resulting in mature lamin A. Point mutation of cytosine to thymine at position 1824 in exon 11 of LMNA gene causes a truncated form of lamin A, which is defined as progerin. In the course of time, progerin is mainly found in skin fibroblasts and reticular layers of terminally differentiated keratinocytes. Changes take place in the nucleus and they are similar to those observed in patients with Hutchinson-Gilford progeria syndrome and refer mainly to an increase in the amount of reactive oxygen species which reduce the level of antioxidant enzymes, DNA damage and histone modification. There are still pending studies on working out new anti-aging strategies and the skin is the main area of research. Biomimetic peptides (analogues of elafin) are used in cosmetics to reduce the formation of progerin

Melanin and lipofuscin as hallmarks of skin aging

Discoloration are symptoms of skin aging. They are connected with presence of melanin and lipofuscin, whose excess and abnormal distribution in the skin cause dark spots to appear. Melanin is formed under the influence of tyrosinase during melanogenesis. Its content changes with age, which may be a result of menopause. Lipofuscin is another example of the age pigment. It is composed of proteins, lipids and carbohydrates. It is described as an age pigment because its content increases with age. The formation and accumulation of lipofuscin is inevitable and leads to cell and homeostasis dysfunction because it reduces the proteasome activity

Effects of reactive oxygen species on skin photoaging

The large surface area of the skin, high metabolism and location at the border of two environments (external and internal) cause continuous production of free radicals within the skin. There are two mechanisms of skin photoaging. The first one involves UVA-induced production of reactive oxygen species. The second mechanism is based on a direct interaction of UVB with DNA and induction of damage in the DNA structure. One way by which UVA leads to skin aging is activation of the AP-1 transcription factor due to singlet oxygen, which is released by UV radiation. Antioxidants slow down oxidation leading to the formation of free radicals, or inactivate already formed free radicals, and thereby accelerate interruption of chain reactions. Moreover, photoprotection has a key role in combating photoaging and eliminating its effects

Effects of reactive oxygen species on skin photoaging

The large surface area of the skin, high metabolism and location at the border of two environments (external and internal) cause continuous production of free radicals within the skin. There are two mechanisms of skin photoaging. The first one involves UVA-induced production of reactive oxygen species. The second mechanism is based on a direct interaction of UVB with DNA and induction of damage in the DNA structure. One way by which UVA leads to skin aging is activation of the AP-1 transcription factor due to singlet oxygen, which is released by UV radiation. Antioxidants slow down oxidation leading to the formation of free radicals, or inactivate already formed free radicals, and thereby accelerate interruption of chain reactions. Moreover, photoprotection has a key role in combating photoaging and eliminating its effects

Biochemical, Structural Analysis, and Docking Studies of Spiropyrazoline Derivatives

In this study, we evaluated the antiproliferative potential, DNA damage, crystal structures, and docking calculation of two spiropyrazoline derivatives. The main focus of the research was to evaluate the antiproliferative potential of synthesized compounds towards eight cancer cell lines. Compound I demonstrated promising antiproliferative properties, especially toward the HL60 cell line, for which IC50 was equal to 9.4 μM/L. The analysis of DNA damage by the comet assay showed that compound II caused DNA damage to tumor lineage cells to a greater extent than compound I. The level of damage to tumor cells of the HEC‐1‐A lineage was 23%. The determination of apoptotic and necrotic cell fractions by fluorescence microscopy indicated that cells treated with spiropyrazoline‐based analogues were entering the early phase of programmed cell death. Compounds I and II depolarized the mitochondrial membranes of cancer cells. Furthermore, we performed simple docking calculations, which indicated that the obtained compounds are able to bind to the PARP1 active site, at least theoretically (the free energy of binding values for compound I and II were −9.7 and 8.7 kcal mol−1, respectively). In silico studies of the influence of the studied compounds on PARP1 were confirmed in vitro with the use of eight cancer cell lines. The degradation of the PARP1 enzyme was observed, with compound I characterized by a higher protein degradation activity