Abstract:
:Mostotrin (MT), a novel compound, at least five orders of magnitude more soluble in water than its mother substance, was designed and synthesised from tryptanthrin (TR). Its structure was established by nuclear magnetic resonance and mass spectrometry data and confirmed by X‑ray analysis, revealing that MT is a pentacyclic product with an additional pseudo‑cycle formed with the participation of one intramolecular hydrogen bond. Antimicrobial activity and cytotoxic action against tumour cells in vitro, as well as anti‑tumour effects, acute toxicity and anti‑inflammatory activities in vivo, were evaluated. Antimicrobial properties of MT against Mycobacterium spp and Bacillus cereus ATCC 10702 appeared to be the same as that of TR, but against the other strains used it was weaker. Furthermore, MT exhibited 5‑10 times higher cytotoxic activities against tumour cell lines HCT‑116, МСF‑7 and K‑562 than TR, but was less toxic than TR (LD50 of MT was 375 mg/kg, while LD50 for TR was 75 mg/kg). Additionally, compounds MT and TR were studied in DNA binding tests. The quenching of its fluorescence on addition to DNA solution established MT to be capable of binding to DNA. Its anti‑tumour action in vivo on mice with the ascitic form of Ehrlich carcinoma was promising, particularly with joint application of MT and the antitumour drug doxorubicin. In this model, the survival and life span for the doxorubicin and 1 co‑treatment group were significantly higher compared to doxorubicin treatment alone. The compound MT showed a lower immunosuppressive effect than TR at the early stages of inflammation induced in mice by LPS from E. сoli (MT hardly inhibited the release of IL‑1, IL‑2, or INF‑γ). These results demonstrated that MT is a perspective hit compound for drug development. In our opinion, further evaluation on the biological effects of MT and its synthetic analogues could lead to safer and more effective anti‑tumour and anti‑tuberculosis agents than TR itself. MT has also the prospect of application in combination with known anti‑tumour drugs for the treatment of oncological diseases.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Popov A,Klimovich A,Styshova O,Moskovkina T,Shchekotikhin A,Grammatikova N,Dezhenkova L,Kaluzhny D,Deriabin P,Gerasimenko A,Udovenko A,Stonik Vdoi
10.3892/ijmm.2020.4693subject
Has Abstractpub_date
2020-10-01 00:00:00pages
1335-1346issue
4eissn
1107-3756issn
1791-244Xjournal_volume
46pub_type
杂志文章abstract::The purpose of this study was to detect the differentially expressed genes between ossified herniated discs and herniated discs without ossification. In addition, we sought to identify a few candidate genes and pathways by using bioinformatics analysis. We analyzed 6 samples each of ossified herniated discs (experimen...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2821
更新日期:2017-01-01 00:00:00
abstract::Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed ch...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2008-09-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and there is an urgent need to identify effective pharmacological strategies to treat NAFLD. For this purpose, in the present study, we examined the the possible molecular mechanisms responsible for the effects of MgIG and the...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2603
更新日期:2016-07-01 00:00:00
abstract::The molecular mechanisms underlying entry of group B Streptococci (GBS) into human endothelial cells are not yet fully understood. This study is centered on the triggering of signaling cascade in human umbilical vein endothelial cells (HUVEC) during their interaction with different GBS serotypes/strains (type III: 803...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-05-01 00:00:00
abstract::Peripheral arterial disease (PAD) affects about 5% of the elderly population in the western world. It has been reported that PAD is associated with elevated plasma levels of the inflammatory markers. The goal of this review is to describe which proinflammatory molecules may play a role in PAD development, C-reactive p...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:
更新日期:2007-09-01 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot a...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2020.4593
更新日期:2020-07-01 00:00:00
abstract::Telomerase activity and hTERT mRNA expression are upregulated in colorectal cancer. Whether they are inherent in colorectal adenomas, premalignant lesions to cancer, however, remains to be elucidated. We examined telomerase activity by the fluorescence-based telomeric repeat amplification protocol method and analyzed ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::Telomerase maintains telomere length and is considered to be necessary for the indefinite proliferation of human cells. Telomerase activity is detected not only in germline and immortal cancer cells, but also in stem/progenitor cells of renewal tissues and activated lymphocytes. While it is generally agreed that telom...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease‑free survival, and...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4284
更新日期:2019-10-01 00:00:00
abstract::Betulinic acid (BA), a potential anticancer compound, could induce apoptosis in human cervical cancer (HeLa) cells, but its mechanism has yet to be fully elucidated. The present study was focused on deciphering the detailed molecular mechanism of BA-induced apoptosis. In the present study, results indicated that BA wa...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3163
更新日期:2017-12-01 00:00:00
abstract::Glucosamine, a naturally occurring amino monosaccharide, is widely used to treat osteoarthritis in humans. Furthermore, glucosamine exhibits an anti-inflammatory action by inhibiting the activation of neutrophils, chondrocytes and synoviocytes. Recently, we revealed that glucosamine suppresses cytokine-induced activat...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2008-09-01 00:00:00
abstract::Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is found to be overexpressed in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the possible role of GPC3 in the development of HCC. In this study, RNA interference (RNAi) with a GPC3 small hairpin RNA (GPC3 shRNA) wa...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.704
更新日期:2011-10-01 00:00:00
abstract::A large number of p53-transcribed proteins have been shown to mediate growth arrest and/or apoptosis in vitro, whereas their in vivo roles remain largely unclear. p53 is capable of initiating apoptosis without transcription of apoptosis inducer genes, although the underlying mechanism is unknown. p53 is present in the...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:
更新日期:2002-01-01 00:00:00
abstract::Determination of CD34+ cells was performed in bone marrow and G-CSF mobilised peripheral blood samples. We adopted three different protocols of analysis: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cell determination and our own protocol based upon the use of PAINT-A-GATEPRO software analysis program....
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.1.1.67
更新日期:1998-01-01 00:00:00
abstract::We have previously reported that the EVn-50 mixture of vitexins (lignan compounds) containing the purified vitexin (neolignan) compound, 6-hydroxy-4(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl‑7-methoxy-3,4-dihydro-2-naphthaldehyde, termed VB1, exhibits potent anticancer activity through the induction of apoptosis in s...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1567
更新日期:2014-02-01 00:00:00
abstract::Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, photosensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS. The BLM protein is homologous to DNA helicase and has two basic amino acid clusters in its C-termina...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.5.5.477
更新日期:2000-05-01 00:00:00
abstract::The elevation of natural killer cell activity (NKCA) by laughter was not confirmed due to incomplete methodology of previous studies although positive emotion is believed to be favorable for health. To verify NKCA elevation by laughter in a crossover design, we measured NKCA before and after watching films, presenting...
journal_title:International journal of molecular medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.3892/ijmm.8.6.645
更新日期:2001-12-01 00:00:00
abstract::POU domain proteins are a family of critical regulators of development and differentiation due to their transcriptional activity in the nucleus. Skn‑1a, a member of the POU domain protein family, appears to be expressed predominantly in epidermal keratinocytes and is thought to play a critical role in keratinocyte dif...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.1803
更新日期:2014-08-01 00:00:00
abstract::In the present study, the effects of erlotinib on mouse tear function and corneal epithelial tissue structure were investigated. Throughout the 3 weeks of treatment, no notable differences were observed in the body, eye or lacrimal gland weights of the control and experimental mice. However, in the experimental group,...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3353
更新日期:2018-03-01 00:00:00
abstract::Choroidal neovascularization (CNV) can lead to progressive and severe visual loss. Vascular endothelial growth factor (VEGF) promotes the development of CNV. Caffeic acid phenethyl ester (CAPE), a biologically active component of the honeybee (Apis mellifera) propolis, has been demonstrated to have several interesting...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2116
更新日期:2015-05-01 00:00:00
abstract::Vascular smooth muscle cell (VSMC) proliferation and migration has been proven to be a critical event in the development of varicosity. Variations in estrogen levels, a pathological event related to age and pregnancy, play a role in the pathogenesis of varicosity. Previous studies have reported a different response of...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2134
更新日期:2015-05-01 00:00:00
abstract::Elastofibroma is a rare, benign, slow-growing degenerative pseudotumor that typically occurs in the subscapular region and has been considered a peculiar fibroblastic proliferation with accumulation of abnormal elastic fibers. Very little is known about the cytogenetic and molecular genetic changes in elastofibroma. I...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::Soy sauce (Shoyu) is a traditional Japanese fermented seasoning and is available worldwide. We investigated the effect of Shoyu polysaccharides (SPS) prepared from soy sauce on the intestinal immune system of mice. SPS enhanced the production of immunoglobulin A (IgA) from Peyer's patch cells in vitro, and its oral ad...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2008-08-01 00:00:00
abstract::Evidence has been recently provided that beacon, an ubiquitin-like protein overexpressed in the hypothalamus of Israeli sand rat, is also expressed in several endocrine glands of the Wistar rat, including adrenal cortex. Moreover, it has been shown that the in vivo administration of beacon[47-73] (hereinafter, beacon)...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies have indicated that understanding the physiological role of autophagy is of great significance. In the present study, an in vitro model was used in which 3T3-L...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2085
更新日期:2015-04-01 00:00:00
abstract::Oxidative stress-induced apoptosis is associated with neuronal cell death and ischemia. The NOL3 [nucleolar protein 3 (apoptosis repressor with CARD domain)] protein protects against oxidative stress-induced cell death. However, the protective mechanism responsible for this effect as well as the effects of NOL3 agains...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2596
更新日期:2016-07-01 00:00:00
abstract::Exendin-4 (ex-4) is a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist which exerts beneficial effects on glycemic control and promotes cell viability. In the present study, we investigated the anti-apoptotic effects of ex-4, as well as the potential mechanisms responsible for these effects in rat bone ma...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2509
更新日期:2016-04-01 00:00:00
abstract::The advanced glycation end‑product (AGE)‑receptor for AGE (RAGE) axis induces transforming growth factor‑β (TGF‑β) expression, cell hypertrophy and increases extracellular matrices that are indicated in the pathogenesis of diabetic nephropathy (DN). RAGE binds to numerous ligands besides AGE, including S100B. In the p...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2024
更新日期:2015-02-01 00:00:00
abstract::The cooperation of liver X receptors (LXRs) alpha and beta, and retinoic X receptor (RXR) modulate the expression of several genes involved in lipid metabolism in hepatocyte and macrophages. Using cDNA microarray technology, we have shown previously that several of these genes are also expressed in endothelial cells. ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-10-01 00:00:00
abstract::Formalin-fixed, paraffin-embedded (FFPE) tissues are one of the popular sources of diagnostic materials, the easiest to store and transport. They are often used as the source of nucleic acids for retrospective molecular analyses based on DNA amplification by polymerase chain reaction (PCR). However, it is known that n...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.8.5.573
更新日期:2001-11-01 00:00:00