Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity.
Ontology highlight
ABSTRACT:
SUBMITTER: Kirsanov K
PROVIDER: S-EPMC9299380 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R(2) = ± 0.0106, R(2)(ajust) = ± 0.0125, s = ± 0.0234, F(4,11) = ± 12.7802, Q(2) = ± 0.0088, SEV = ± 0.0132, PRESS = ± 0.4808 and SPRESS = ± 0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (P(Skin)), plasma protein binding (PPB) and penetration of the blood-brain barrier (C(Brain/Blood)), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.
| S-EPMC6271355 | biostudies-other
Project description:Background: Antimalarials have anticancer potential. Results: We have systematically tested five distinct antimalaria drugs in a panel of cancer cell lines. Conclusion: Three antimalarial classes display potent antiproliferative activity, and their potency is correlated with cancer cell gene expression patterns. Significance: We confirm and extend anticancer potential of these antimalarials and we discuss their therapeutic potential based on clinical data. Key words: Malaria, Anticancer drug, Drug Discovery, Genomics, Gene Expression, Bioinformatics, Cancer AffymetrixM-BM-. HG-U133 Plus 2.0 mRNA expression arrays were used to determine the expression. CEL result files were pre-processed using the RMA (Irizarry et al, 2003) algorithm. This microarray analysis was performed for 91 cell lines.
2013-10-26 | E-GEOD-51739 | biostudies-arrayexpress
Project description:Natural compounds obtained from plants are capable of garnering considerable attention from the scientific community, primarily due to their ability to check and prevent the onset and progress of cancer. These natural compounds are primarily used due to their nontoxic nature and the fewer side effects they cause compared to chemotherapeutic drugs. Furthermore, such natural products perform even better when given as an adjuvant along with traditional chemotherapeutic drugs, thereby enhancing the potential of chemotherapeutics and simultaneously reducing their undesired side effects. Curcumin, a naturally occurring polyphenol compound found in the plant Curcuma longa, is used as an Indian spice. It regulates not only the various pathways of the immune system, cell cycle checkpoints, apoptosis, and antioxidant response but also numerous intracellular targets, including pathways and protein molecules controlling tumor progression. Many recent studies conducted by major research groups around the globe suggest the use of curcumin as a chemopreventive adjuvant molecule to maximize and minimize the desired effects and side effects of chemotherapeutic drugs. However, low bioavailability of a curcumin molecule is the primary challenge encountered in adjuvant therapy. This review explores different therapeutic interactions of curcumin along with its targeted pathways and molecules that are involved in the regulation of onset and progression of different types of cancers, cancer treatment, and the strategies to overcome bioavailability issues and new targets of curcumin in the ever-growing field of cancer.
| S-EPMC5386596 | biostudies-literature
Project description:Background: Antimalarials have anticancer potential. Results: We have systematically tested five distinct antimalaria drugs in a panel of cancer cell lines. Conclusion: Three antimalarial classes display potent antiproliferative activity, and their potency is correlated with cancer cell gene expression patterns. Significance: We confirm and extend anticancer potential of these antimalarials and we discuss their therapeutic potential based on clinical data. Key words: Malaria, Anticancer drug, Drug Discovery, Genomics, Gene Expression, Bioinformatics, Cancer
2013-10-26 | GSE51739 | GEO
Project description:Porcupine bezoars (PBs) are masses of undigested calcareous concretions formed within the gastrointestinal tract. There are undocumented claims that PBs have antioxidant activity and can treat cancers. However, limited scientific study has been carried out to verify these traditional claims. Hence, this study was conducted to characterize the chemical profile and validate the antioxidant and anticancer activity against melanoma cells (A375). PB extract was initially subjected to Fourier-transform infrared spectroscopy (FTIR), gas chromatography?mass spectrometry (GCMS), total phenolic content (TPC), and total flavonoid content (TFC) analyses. The bioautography of antioxidant assays, namely 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazy (DPPH), and ?-carotene was performed. An in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, and gene expression assay were carried out as well. The experimental finding revealed 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a:1',2'-d]pyrazine, ursodeoxycholic acid, and cholest-5-en-3-ol (3 beta)-, carbonochloridate are major compounds detected in PB extract. PB extract has low phenolic content, viz. 698.7 ± 0.93 (µg GAE/5 mg dry weight). The bioautography antioxidant assays revealed a potent antioxidant effect (ABTS > DPPH > ?-carotene), with free radical scavenging activity. Furthermore, PB extract exhibited dose- and time-dependent inhibition of cancer activity on A375 cells due to the exhibition of apoptosis via an intrinsic pathway.
| S-EPMC6406421 | biostudies-literature
Project description:As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA) in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer.
| S-EPMC5307245 | biostudies-literature
Project description:The addition of 2-amino-1,3,4-thiadiazole derivatives with parallel iodination of differently protected glycals has been achieved using a double molar excess of molecular iodine under mild conditions. The corresponding thiadiazole derivatives of N-glycosides were obtained in good yields and anomeric selectivity. The usage of iodine as a catalyst makes this method easy, inexpensive, and successfully useable in reactions with sugars. Thiadiazole derivatives were tested in a panel of three tumor cell lines, MCF-7, HCT116, and HeLa. These compounds initiated biological response in investigated tumor models in a different rate. The MCF-7 is resistant to the tested compounds, and the cytometry assay indicated low increase in cell numbers in the sub- G1 phase. The most sensitive are HCT-116 and HeLa cells. The thiadiazole derivatives have a pro-apoptotic effect on HCT-116 cells. In the case of the HeLa cells, an increase in the number of cells in the sub-G1- phase and the induction of apoptosis was observed.
| S-EPMC8659227 | biostudies-literature
Project description:Fungi are ubiquitous, they proliferate even in environments with toxic pollutants that are otherwise harmful to other eukaryotes. This article presents data of fungi which were isolated from gold mine tailings and identified by DNA sequencing of their inter transcribed spacer regions 1 and 2. Five fungal isolates were identified, among which the crude extract of Penicillium janthinellum KTMT5 was investigated for anticancer activity on A549 (lung carcinoma) and UMG87 (glioblastoma) cell lines. Untargeted metabolite profiling of the crude extract of P. janthinellum KTMT5 was performed using liquid chromatography quadrupole time of flight tandem mass spectrometry (LC-QTOF-MS/MS) and a molecular network generated using the online workflow on the Global Natural Product Social molecular networking (GNPS) website. DNA sequencing showed that all fungal isolates belonged to phylum Ascomycota with the genus Penicillium representing 75% of the fungal isolates. P. janthinellum KTMT5 which was selected for further experiments showed significant anticancer activity against UMG87 cells with a calculated IC50 value of 44.23 ?g/mL in the MTS assay, while the real time xCELLigence assay showed dose-dependent anticancer activity at 50 and 100 ?g/mL. Metabolite profiling revealed the presence of several known metabolites in the crude extract of P. janthinellum KTMT5 and molecular networking showed the relationships among these metabolites.
| S-EPMC6928313 | biostudies-literature
Project description:Plectranthus species (Lamiaceae) have been employed in traditional medicine and this is now validated by the presence of bioactive abietane-type diterpenoids. Herein, sixteen Plectranthus acetonic extracts were prepared by ultrasound-assisted extraction and their biological activity was screened. The antimicrobial activity of each extract was screened against yeasts, and Gram-positive and Gram-negative bacteria. The P. hadiensis and P. mutabilis extracts possessed significant activity against Staphylococcus aureus and Candida albicans (microdilution method). Moreover, all extracts showed antioxidant activity using the DPPH method, with P. hadiensis and P. mutabilis extracts having the highest scavenging activities. Selected by the Artemia salina model, P. hadiensis and P.ciliatus possessed low micromolar anti-proliferative activities in human colon, breast, and lung cancer cell lines. Furthermore, the most bioactive extract of P. hadiensis leaves and the known abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone isolated from this plant, were tested against the aggressive type triple negative breast cancer (MDA-MB-231S). P. hadiensis extract reduced the viability of MDA-MB-231S cancer cell line cells, showing an IC50 value of 25.6 µg/mL. The IC50 value of 7α-acetoxy-6β-hydroxyroyleanone was 5.5 µM (2.15 µg/mL), suggesting that this lead molecule is a potential starting tool for the development of anti-cancer drugs.
| S-EPMC8146581 | biostudies-literature
Project description:Background: Tyrosine kinase inhibitors (TKIs) are widely used for treating solid and hematologic malignancies. However, their efficacy is frequently short lived, warranting the search for safe potentiation strategies. Short courses of fasting were shown to sensitize cancer cells to chemo- and radiotherapy while increasing the resistance of healthy tissues to the same agents. The purpose of this study was to assess the potential of fasting to increase the efficacy of TKIs. Methods: starvation-mimicking culture conditions were studied for their ability to potentiate the effects of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Anaplastic Lymphoma Kinase (ALK) and multitarget TKIs in terms of cancer cell growth, signaling cascades inhibition, and changes in gene expression profile in TKI-sensitive cancer cells. In vivo, the activity of crizotinib or regorafenib, weekly cycles of fasting, or their combination was compared in tumor xenografts models. Results: In vitro, starvation-mimicking culture conditions increased the ability of TKIs to block cancer cell growth and to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway. At the gene expression profile level, starvation and crizotinib led to similar changes, but their combination strengthened Rb-, MYC-, and E2F-dependent transcription inhibition. In vivo, both TKIs and cycles of fasting slowed tumor growth, but, when combined, they were significantly more effective than either type of treatment alone. Conclusions: Cycles of fasting or of specifically designed fasting-mimicking diets should be evaluated in clinical studies as a means to potentiate the activity of TKIs in clinical use. RNA was collected from H3122 cells in 4 different conditions: serum, starvation, treated with Crizotinib, starvation and treated with Crizotinib. Each condition was run in quadruplicate
2016-07-03 | E-GEOD-62663 | biostudies-arrayexpress