Ehimen Annastasia Erazua

Bio: Ehimen Annastasia Erazua is an academic researcher from University of Ibadan. The author has contributed to research in topics: Docking (molecular) & Quantitative structure–activity relationship. The author has an hindex of 1, co-authored 2 publications receiving 3 citations.

DFT-QSAR and Molecular Docking Studies on 1,2,3-Triazole-Dithiocarbamate Hybrids as Potential Anticancer Agents

Abstract: Recently, considerable attention has been drawn on the search for novel anticancer drugs in order to improve survival rates and wellbeing of cancer patients. 1,2,3-triazole is an attractive scaffold possessing diverse biological activities. The quantitative structure–activity relationship (QSAR) is a powerful computational tool which has widened the scope of rational drug design, as well as the search for the mechanisms of drug actions. A series of novel 1,2,3-triazole-dithiocarbamate hybrids (1,2,3-TDHs) were studied for anticancer activity against human gastric cancer cell line (MGC-803) using Density Functional Theory (DFT), Quantitative Structure Activity Relation (QSAR) and Docking approaches. QSAR models were successfully constructed with acceptable predictive performance. The QSAR analysis indicated that certain molecular descriptors namely EHOMO, Original Research Article Erazua et al.; PSIJ, 20(4): 1-10, 2018; Article no.PSIJ.46207 2 ELUMO, Log P, Area, the total electronic charges on the heteroatom (H), and the average electronic charge on the heteroatoms (H_HET4r) are important factors for the observed biological activity. The results from docking study predicted stable conformations of the ligands within the enzyme’s active gouge of the receptor. Compound E, tert Butyl 4-(((1-(4-methylbenzyl)-1H-1,2,3triazol-4-yl)methylthio)carbonothioyl)-piperazine-1-arboxylate, formed the most stable complex with the protein receptor.

DFT and Molecular Docking Investigation of Potential Anticancer Properties of Some Flavonoids

Abstract: There is a continuous need to discover and obtain more efficient drug-like molecule to suppress cancer in human being. Recently researchers are using molecular docking technique to improve the understanding of the interaction between drug and receptor, in other to obtain novel drugs for more efficient usage. Anticancer activities of some selected flavonoids were studied using quantum chemical method through Density Functional Theory (DFT) and molecular docking approach. These Flavoniods were docked against breast cancer cell line (3s7s) using Autodock tool, AutoDockVina as docking tools and Biovia Discovery Studio 2017 for post docking analysis. The binding affinity obtained was used to correlate the inhibitory activity of these flavoniods with their calculated molecular descriptors. The obtained binding energy showed that quercetin has the highest inhibition efficiency hence it has the highest ability to inhibit 3s7s than other studied compounds. It was observed that some molecular descriptor such as band gap, dipole moment, logP and E HOMO , were significant to the inhibiting ability of quercetin in the active site of the protein.

Quantitative Structure-Activity relationship, Molecular Docking and ADMET Screening of Tetrahydroquinoline Derivatives as Anti-Small Cell Lung Cancer Agents

Abstract: Lung carcinoma (LC) is responsible for almost one-third of all cancer fatalities worldwide. Tetrahydroquinoline is an organic molecule that is the semi-hydrogenated derivative of quinoline and could be found in several naturally occurring compounds such as flindersine, oricine etc. Some tetrahydroquinoline derivatives with pyrazole and hydrazide moieties were evaluated in silico against A549 (human lung cancer cell lines). The quantitative structural-activity relationship (QSAR) model created was statistically significant with validation metrics of R2 (0.9525), R2adj (0.9314), and CV.R (0.9719). The molecular docking analysis revealed that compound C14 demonstrated the best binding affinity towards the studied protein with binding affinity value of –10.1 kcal mol–1 (4LRM). This is in accordance with the experimental result (IC50 = 0.69). The factors observed for ADME&T correlated well with the factors observed for the referenced drug. This study indicates that compounds C1 and C9 can be further developed as anti-epidermal growth factor receptor (EGFR) compounds. Thus, our findings may open door for the design and development of library of efficient Tetrahydroquinoline-based drug-like compounds as potential anti-LC agents.

Theoretical and Spectroscopic Characterization of API-Related Azoles in Solution and in Solid State.

Abstract: Azoles are a family of five-membered azacyclic compounds with relevant biological and pharmacological activity. Different subclasses of azoles are defined depending on the atomic arrangement and the number of nitrogen atoms present in the ring: pyrazoles, indazoles, imidazoles, benzimidazoles, triazoles, benzotriazoles, tetrazoles and pentazoles. The complete characterization of their structure and the knowledge about their crystal packing and physical and chemical properties are of vital importance for the advancement in the design of new azole-containing drugs. In this review, we report the latest recent contributions to azole chemistry, in particular, those in which theoretical studies have been performed.

Flavonoids

Abstract: Flavonoids, defined as plant-derived secondary metabolites, have been widely found in nature with more than 10,000 different species, since their discovery. They are divided into subclasses based on the oxidative state of the ring, such as flavones, flavonols, flavanones, isoflavones, flavandiols, dihydroflavonols, and anthocyanidins. They are promising compounds with a wide variety of biological activities including antioxidant, antitumor, antigen-toxicity properties. Furthermore, flavonoids are seen as promising tools in the development of new drug assets, and they have been the subject of studies for the development of high-efficiency formulations for the treatment of a variety of future-threatening diseases. Molecular modeling studies play an important role in identifying the most stable molecular configurations and conformations of these molecules. This chapter focuses on the structural and functional properties of flavonoids, their biological activities, bioavailability, use in cancer, use in the development of new drugs, and molecular modeling studies on these molecules.

Cyclic RGD-containing peptides: in silico exploration against BCL-X(L)

Abstract: Сyclic peptides attract attention for possible applications in cancer treatment. We examined the abili­ty of six cyclic RGD-containing peptides-based compounds to inhibit B-cell lymphoma-extra-large (Bcl-XL) (PDB ID: 3zk6) using the in silico method. We observed that the addition of electron withdrawing group (–Cl) to cyclic RGD-containing peptides-based compound induced a radical improvement in the hydrogen bond strength with Arg139 in Bcl-XL. Compound F with -9.2 kcal/mol was observed to be positioned at the best-docked site in the binding pocket of Bcl-XL and therefore suggested to have greater potential anticancer abili­ty than other studied compounds as well as the referenced compound (Doxorubicin). The ADMET properties of compound F and Doxorubicin were investigated and reported. Our findings may open door for the design and development of library of efficient cyclic RGD-containing peptides-based drug-like compounds as potential anti- cancer agents. Keywords: Bcl-X(L), carcinogesis, cyclic RGD peptides, in silico study, modeling­, peptide-protein interaction