scholarly journals Design of New Chlorochalcone Derivatives as Potential Breast Anticancer Compound Based on QSAR Analysis and Molecular Docking Study

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Anita Dwi Puspitasari ◽  
Harno Dwi Pranowo ◽  
Endang Astuti ◽  
Tutik Dwi Wahyuningsih
Keyword(s):  
Molecular Docking ◽  
Correlation Coefficient ◽  
Biological Activities ◽  
Basis Set ◽  
Log P ◽  
Anticancer Activities ◽  
Mcf7 Cells ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
Cox 2

Quantitative structure-activity relationships (QSAR) proposes a model that relates the biological activities of drugs to their chemical structures, and the interaction between the drug and its target enzyme is revealed by molecular docking research. These studies were conducted on chalcone to produce a model that could design highly potent breast anticancer MCF7 cells. The compounds were optimized using ab initio using a basis set 6-31G, then their descriptors calculated using this method. Genetic Function Algorithm (GFA) was used to select descriptors and build the model. One of the six models generated was found to be the best with internal and external squared correlation coefficient (R2) of 0.743 and 0.744, respectively, adjusted squared correlation coefficient (adjusted R2) of 0.700, Standard estimate of error (SEE) of 0.198, Fcalc/Ftable of 6.423, and Predicted residual sum of squares (PRESS) of 1.177. The QSAR equation is pIC50 = 3.869 + (1.427 x qC1) + (4. 027 x qC10) + (0.856 x qC15) - (35.900 x ELUMO) + (0.208 x Log P). Hence, it can predict the breast anticancer activities of new chlorochalcones A-F. The compound with the best prediction was chlorochalcone A with pIC50 2.65 and IC50 value of 2.26 μM. The chlorochalcones A-F were able to bind to the main amino acid residues, namely Arg120 and Tyr355, on the active site of the COX-2 enzyme. These results could serve as a model for designing novel chlorochalcone as inhibitors of COX-2 with higher breast anticancer activities. Keywords: Chlorochalcone, COX-2, QSAR, MCF-7, Molecular docking

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Computational Study of Geometry, Polarizability, Hyperpolarizability and Molecular Docking Studies of Naproxen

2016 ◽  
Vol 15 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Sharmin Aktar ◽  
Mohammad Firoz Khan ◽  
Muhammed Mahfuzur Rahman ◽  
Mohammad A Rashid
Keyword(s):  
Molecular Docking ◽  
Computational Study ◽  
Solvent Polarity ◽  
Docking Study ◽  
Polarizable Continuum Model ◽  
Docking Studies ◽  
Basis Set ◽  
Mulliken Charge ◽  
Molecular Docking Study ◽  
Cox 2

A computational assessment of geometry, molecular electrostatic potential (MESP), Mulliken charge distribution, polarizability, hyperpolarizability and molecular docking study of naproxen with human COX-2 enzyme were conducted. B3LYP level of theory using 6-31G(d,p) basis set was used to optimize the structure of naproxen. The default Polarizable Continuum Model (PCM) of Gaussian09 software was applied for all calculations involving solvents, water and n-octanol. Almost all bond lengths and angles of naproxen agree very well with the X-ray crystal structure suggesting that the molecule is well described with B3LYP/6-31G(d,p) level of theory. The polarizability and first order hyperpolarizability were increased with the increase of solvent polarity. Moreover, docking study revealed that naproxen interacts with human COX-2 enzyme at a binding affinity of -8.2 kcal/mol forming one hydrogen bond with TYR354.Dhaka Univ. J. Pharm. Sci. 15(1): 37-45, 2016 (June)

Preliminary Identification of Hamamelitannin and Rosmarinic Acid as COVID-19 Inhibitors Based on Molecular Docking

2020 ◽  
Vol 17 ◽  
Author(s):  
Kaushik Sarkar ◽  
Rajesh Kumar Das
Keyword(s):  
Molecular Docking ◽  
Rosmarinic Acid ◽  
Virus Disease ◽  
Binding Energies ◽  
Basis Set ◽  
Global Public Health ◽  
Molecular Docking Study ◽  
Ligand Interaction ◽  
Chemical Structures ◽  
Protein Ligand Interaction

Background: Recently novel corona virus disease, COVID-19 caused the outbreak situation of global public health. In this pandemic situation, all the people lives of 212 Countries and Territories have been affected due to partial or complete lockdown and also as a result of mandatory isolations or quarantines. This is due to the non-availability of any secure vaccine. Objective: The present study helps us to identify and screen best phytochemicals as potent inhibitors against COVID-19. Methods: In this paper we choose two standard drugs namely hamamelitannin and rosmarinic acid as a probable inhibitor of pandemic COVID-19 receptor as compared to antimalarial drug hydroxychloroquine, anti-viral drug remdesivir and also baricitinib. This study was done by taking into consideration of molecular docking study, performed with Auto Dock 4.0 (AD4.0). All chemical structures were optimized with Avogadro suite by applying MMFF94 force field and also hamamelitannin, rosmarinic acid were optimized using Gaussian G16 suite of UB3LYP/6-311++G(d,p) basis set. Protein-ligand interaction was visualized by PyMOL software. Results and Discussion: This work has provided an insightful understanding of protein-ligand interaction of hamamelitannin and rosmarinic acid showing comparable binding energies than that of clinically applying probable COVID-19 inhibitors hydroxychloroquine (an anti-malarial drug) and remdesivir (an anti-viral drug). Conclusions: We will expect that if its anti-SARS-CoV-2 activity is validated in human clinical trials, these two drugs may be developed as an effective antiviral therapeutics towards infected patients in this outbreak and pandemic situation of COVID-19.

scholarly journals Biological Evaluation and Molecular Docking Studies of Dimethylpyridine Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1093 ◽  
Author(s):  
Piotr Świątek ◽  
Katarzyna Gębczak ◽  
Tomasz Gębarowski ◽  
Rafal Urniaz
Keyword(s):  
Molecular Docking ◽  
Biological Evaluation ◽  
In Vivo Studies ◽  
Cyclooxygenase Inhibitors ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Cox 2 ◽  
Cox 1

Cyclooxygenase inhibitors as anti-inflammatory agents can be used in chemoprevention. Many in vitro and in vivo studies on human and animal models have explained the mechanisms of the chemopreventive effect of COX inhibitors such as: induction of apoptosis, inhibition of neoplasia, angiogenesis suppression, induction of cell cycle inhibition and inhibition of the expression of peroxisome proliferator-activated receptors. Here, biological evaluation of twelve different Schiff base derivatives of N-(2-hydrazine-2-oxoethyl)-4,6-dimethyl-2-sulfanylpyridine- 3-carboxamide are presented. Their in vitro anti-COX-1/COX-2, antioxidant and anticancer activities were studied. The molecular docking study was performed in order to understand the binding interaction of compounds in the active site of cyclooxygenases. Compounds PS18 and PS33 showed a significant inhibitory activity on COX-1 at lower concentrations compared to meloxicam and piroxicam. The IC50 of COX-1 of these compounds was 57.3 µM for PS18 and 51.8 µM for PS33. Out of the tested compounds, the highest therapeutic index was demonstrated by PS18, PS19, PS33, PS40 and PS41. Lower molar concentrations of these compounds inhibit the growth of cancer cells while not inhibiting the healthy cells. Compounds PS18, PS19 and PS33 simultaneously demonstrated a statistically-significant inhibition of COX-1 or COX-2. This opens up the possibility of applying these compounds in the chemoprevention of cancer.

Cardenolides and pentacyclic triterpenes isolated from Acokanthera oblongifolia leaves: their biological activities with molecular docking study

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Howaida I. Abd-Alla ◽  
Maha M. Soltan ◽  
Amal Z. Hassan ◽  
Hanan A. A. Taie ◽  
Heba M. Abo-Salem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Topoisomerase I ◽  
Biological Activities ◽  
Molecular Docking Study ◽  
2D Nmr Spectroscopy ◽  
Binding Interaction ◽  
Pentacyclic Triterpenes ◽  
Chemical Structures ◽  
H5n1 Influenza

Abstract Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Their chemical structures were determined based on comprehensive 1D and 2D NMR spectroscopy. Their MIC was determined against 12 microorganisms. Their exerted cytotoxicity on the immortalized normal cells, hTERT-RPE1 was assessed by the sulforhodamine-B assay. The viral inhibitory effects of compounds against Newcastle disease virus (NDV) and H5N1 influenza virus IV were evaluated. Four in vitro antioxidant assays were performed in comparison with BHT and trolox and a weak activity was exhibited. Acovenoside A was with potent against H5N1-IV and NDV with IC50 ≤ 3.2 and ≤ 2.1 μg/ml and SI values of 93.75 and 95.23%, respectively, in comparison to ribavirin. Its CC50 record on Vero cells was > 400 and 200 μg/ml, respectively. Acobioside A was the most active compound against a broad range of microbes while Pseudomonas aeruginosa was the most sensitive. Its MIC (0.07 μg/ml) was 1/100-fold of the recorded CC50 (7.1 μg/ml/72 h) against hTERT-RPE1. The molecular docking of compounds on human DNA topoisomerase I (Top1-DNA) and IV glycoprotein hemagglutinin were studied using MOE program. This study has introduced the cardenolides rather than triterpenoids with the best docking score and binding interaction with the active site of the studied proteins.

scholarly journals Density Functional Theory and Molecular Docking Investigations of the Chemical and Antibacterial Activities for 1-(4-Hydroxyphenyl)-3-phenylprop-2-en-1-one

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3631
Author(s):  
Ahmed M. Deghady ◽  
Rageh K. Hussein ◽  
Abdulrahman G. Alhamzani ◽  
Abeer Mera
Keyword(s):  
Density Functional Theory ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Carbonyl Group ◽  
Active Sites ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Basis Set ◽  
Molecular Docking Study ◽  
Functional Theory

The present investigation informs a descriptive study of 1-(4-Hydroxyphenyl) -3-phenylprop-2-en-1-one compound, by using density functional theory at B3LYP method with 6-311G** basis set. The oxygen atoms and π-system revealed a high chemical reactivity for the title compound as electron donor spots and active sites for an electrophilic attack. Quantum chemical parameters such as hardness (η), softness (S), electronegativity (χ), and electrophilicity (ω) were yielded as descriptors for the molecule’s chemical behavior. The optimized molecular structure was obtained, and the experimental data were matched with geometrical analysis values describing the molecule’s stable structure. The computed FT-IR and Raman vibrational frequencies were in good agreement with those observed experimentally. In a molecular docking study, the inhibitory potential of the studied molecule was evaluated against the penicillin-binding proteins of Staphylococcus aureus bacteria. The carbonyl group in the molecule was shown to play a significant role in antibacterial activity, four bonds were formed by the carbonyl group with the key protein of the bacteria (three favorable hydrogen bonds plus one van der Waals bond) out of six interactions. The strong antibacterial activity was also indicated by the calculated high binding energy (−7.40 kcal/mol).

Synthesis of a Series of Novel 2-Amino-5-Substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole Derivatives as Potential Anticancer, Antifungal and Antibacterial Agents

2021 ◽  
Vol 17 ◽  
Author(s):  
Em Canh Pham ◽  
Tuyen Ngoc Truong ◽  
Nguyen Hanh Dong ◽  
Duy Duc Vo ◽  
Tuoi Thi Hong Do
Keyword(s):  
Cell Line ◽  
Biological Activities ◽  
Chemical Properties ◽  
Diffusion Method ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
Antifungal Activities ◽  
Antibacterial And Antifungal Activities ◽  
Thiadiazole Derivatives ◽  
Antibacterial And Antifungal

Background: Many compounds containing a five-membered heterocyclic ring display exceptional chemical properties and versatile biological activities. Objective: The objective of the present study was the desire to prepare the 5-substituted 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole derivatives and evaluate their potential anticancer, antibacterial and antifungal activities. Methods: Twenty-seven derivatives were synthesized by iodine-mediated cyclization of semicarbazones or thiosemicarbazones obtained from condensation of semicarbazide or thiosemicarbazide and aldehydes. The structures were confirmed by 1H-NMR, 13C-NMR and MS spectra. The antibacterial and antifungal activities were evaluated by diffusion method and the anticancer activities were evaluated by MTT assay. Results: Twenty-seven derivatives have been synthesized in moderate to good yields. A number of derivatives exhibited potential antibacterial, antifungal and anticancer activities. Conclusion: Compounds (1b, 1e and 1g) showed antibacterial activity against Streptococcus faecalis, MSSA and MRSA with MIC ranging between 4 to 64 µg/mL. Compound (2g) showed antifungal activity against Candida albicans (8 µg/mL) and Aspergillus niger (64 µg/mL). Compound (1o) exhibited high cytotoxic activity against HepG2 cell line (IC50 value 8.6 µM), which is comparable to the activity of paclitaxel, and is non-toxic on LLC-PK1 normal cell line. The structure activity relationship and molecular docking study of the synthesized compounds are also reported.

scholarly journals Terpenoids and Their Biological Activities from Cinnamomum: A Review

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Meiting Wu ◽  
Lin Ni ◽  
Haixiao Lu ◽  
Huiyou Xu ◽  
Shuangquan Zou ◽  
...  
Keyword(s):  
Biological Activities ◽  
Biological Effects ◽  
Pharmacological Effects ◽  
Bioactive Components ◽  
Anticancer Activities ◽  
Chemical Structures ◽  
The Family ◽  
Beneficial Uses ◽  
The Future ◽  
Depth Study

Cinnamomum is a genus of the family Lauraceae, which has been recognized worldwide as an important genus due to its beneficial uses. A great deal of research on its phytochemistry and pharmacological effects has been conducted. It is noteworthy that terpenoids are the characteristic of Cinnamomum due to the peculiar structures and significant biological effects. For a more in-depth study and the better use of Cinnamomum plants in the future, the chemical structures and biological effects of terpenoids obtained from Cinnamomum were summarized in the present study. To date, a total of 181 terpenoids with various skeletons have been isolated from Cinnamomum. These compounds have been demonstrated to play an important role in immunomodulatory, anti-inflammatory, antimicrobial, antioxidant, and anticancer activities. However, studies on the bioactive components from Cinnamomum plants have only focused on a dozen species. Hence, further studies on the potential pharmacological effects need to be conducted in the future.

COX-1/COX-2 inhibition activities and molecular docking study of newly designed and synthesized pyrrolo[3,4-c]pyrrole Mannich bases

2019 ◽  
Vol 27 (17) ◽  
pp. 3918-3928 ◽  
Author(s):  
Aleksandra Redzicka ◽  
Łukasz Szczukowski ◽  
Andrzej Kochel ◽  
Benita Wiatrak ◽  
Katarzyna Gębczak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Mannich Bases ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Cox 1
Sign in / Sign up

Export Citation Format

Share Document