4 research outputs found
Development of Virtual Screening and In Silico Biomarker Identification Model for Pharmaceutical Agents
Ph.DDOCTOR OF PHILOSOPH
Oncogene and Cancer
This book describes a course of cancer growth starting from normal cells to cancerous form and the genomic instability, the cancer treatment as well as its prevention in form of the invention of a vaccine. Some diseases are also discussed in detail, such as breast cancer, leucaemia, cervical cancer, and glioma. Understanding cancer through its molecular mechanism is needed to reduce the cancer incidence. How to treat cancer more effectively and the problems like drug resistance and metastasis are very clearly illustrated in this publication as well as some research result that could be used to treat the cancer patients in the very near future. The book was divided into six main sections: 1. HER2 Carcinogenesis: Etiology, Treatment and Prevention; 2. DNA Repair Mechanism and Cancer; 3. New Approach to Cancer Mechanism; 4. New Role of Oncogenes and Tumor Suppressor Genes; 5. Non Coding RNA and Micro RNA in Tumorigenesis; 6. Oncogenes for Transcription Factor
Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.
Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive
compounds
Energy-Based Pharmacophore and Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR) Modeling Combined with Virtual Screening To Identify Novel Small-Molecule Inhibitors of Silent Mating-Type Information Regulation 2 Homologue 1 (SIRT1)
Silent
mating-type information regulation 2 homologue 1 (SIRT1),
being the homologous enzyme of silent information regulator-2 gene
in yeast, has multifaceted functions. It deacetylates a wide range
of histone and nonhistone proteins; hence, it has good therapeutic
importance. SIRT1 was believed to be overexpressed in many cancers
(prostate, colon) and inflammatory disorders (rheumatoid arthritis).
Hence, designing inhibitors against SIRT1 could be considered valuable.
Both structure-based and ligand-based drug design strategies were
employed to design novel inhibitors utilizing high-throughput virtual
screening of chemical databases. An energy-based pharmacophore was
generated using the crystal structure of SIRT1 bound with a small
molecule inhibitor and compared with a ligand-based pharmacophore
model that showed four similar features. A three-dimensional quantitative
structure–activity relationship (3D-QSAR) model was developed
and validated to be employed in the virtual screening protocol. Among
the designed compounds, <b>Lead 17</b> emerged as a promising
SIRT1 inhibitor with IC<sub>50</sub> of 4.34 μM and, at nanomolar
concentration (360 nM), attenuated the proliferation of prostate cancer
cells (LnCAP). In addition, <b>Lead 17</b> significantly reduced
production of reactive oxygen species, thereby reducing pro inflammatory
cytokines such as IL6 and TNF-α. Furthermore, the anti-inflammatory
potential of the compound was ascertained using an animal paw inflammation
model induced by carrageenan. Thus, the identified SIRT1 inhibitors
could be considered as potent leads to treat both cancer and inflammation