Synthesis, antineoplastic activity and in silico studies of (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-tolyl)-1,2,4-oxadiazole-5-carboxamide

2021 ◽  
Vol 25 (7) ◽  
pp. 167-176
Author(s):  
Cláudia Laís Araújo Almeida Santos ◽  
Jonh Anderson Macêdo Santos ◽  
Rodrigo Ribeiro Alves Caiana ◽  
Silvia Maria Souza ◽  
Jucleiton José Rufino Freitas ◽  
...  
Keyword(s):  
In Silico ◽  
Low Cost ◽  
Docking Study ◽  
New Drugs ◽  
Molecular Docking Study ◽  
Traditional Medicines ◽  
In Silico Studies ◽  
In Silico Study ◽  
Pharmacokinetic Properties ◽  
Low Toxicity

The development of chemotherapy agents without side effects is a major challenge, since traditional medicines usually have undesirable properties such as high toxicity, resistance and low bioavailability. In this sense, computational methods play a crucial role in the discovery and optimization of new drugs, as they combine speed and efficiency with low cost. The 1,2,4-oxadiazoles are one of the main classes of heterocyclics due to their numerous biological applications. In this work, we report the synthesis, antineoplastic evaluation and in silico study of a new 1,2,4-oxadiazole. The (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-toluyl)-1,2,4-oxadiazole-5-carboxamide was obtained after two reaction steps in excellent yield. Although it has shown low activity in relation to the MCF-7, HCT116 and HL60 tumor cell lines, the molecular docking study indicates that this compound acts in the colchicine site and can inhibit tubulin polymerization. From the calculation of pharmacokinetic properties by the SwissADME and Osiris Property Explorer programs, it is possible to infer that the compound meets the Lipinski rules presenting good oral bioavailability and low toxicity.

scholarly journals In silico Study of the Interactions between Schiff Base Polyphenols and HPV 16 E6/E6AP/p53 complex

2021 ◽  
pp. 3973-3980
Author(s):  
Jeremiah I. Ogah ◽  
Olatunji M. Kolawole ◽  
Steven O. Oguntoye ◽  
Muhammed Mustapha Suleiman
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
In Silico ◽  
In Silico Analysis ◽  
Docking Study ◽  
Hydrogen Atoms ◽  
Molecular Docking Study ◽  
Hpv 16 ◽  
In Silico Study

The rise in the incidence of cervical cancer globally has accentuate attention to the potential role of polyphenols as anticancer agents. Different studies have demonstrated the role of some polyphenols in altering Human Papillomavirus (HPV) carcinogenesis. Thus, this study was aimed at establishing the potentials of Schiff-based polyphenols from imesatin and satin as anticancer agents through in silico analysis. The polyphenols were synthesized and characterized using elemental analyses, spectroscopic analyses, UV-visible, Infrared, and Nuclear Magnetic Resonance (1H NMR and 13C, NMR). Molecular docking study of the polyphenols was carried out using Auto Dock Vina. The oncogenic E6 protein structure of HPV 16 was obtained from the protein bank (ID: 4XR8). The E6 proteins were prepared using AutoDock tools. Water molecules were removed from the protein molecules while hydrogen atoms were added. Also, the structures of Curcumin and Isomericitrin were obtained from PubChem. Results showed that three different Schiff based polyphenols were obtained from the synthesis; 3-(2’,4’-dimethoxy benzylidene hydrazono) indoline-2-one (DMBH), 3-(2’-hydroxy-4’-methoxy benzylidene hydrazono) indoline-2-one (HMBD), and 3-((4-4’-((2’’, 4’’-dimethoxy benzylidene amino) benzyl)phenyl)imino) indoline-2-one (DMBP). Higher ability of the docked polyphenols to bind to the E6/E6AP/p53 complex when compared to Curcumin was revealed. Also, results showed that the binding energy of Curcumin and Isomericitrin were -7.1kcal/mol and -8.4kcal/mol respectively while that of the polyphenols ranged from -7.4kcal/mol to -7.9kcal/mol. The molecular docking results of the polyphenols used in this study further confirm their potentials as strong anti-cancer agents.

scholarly journals Chrysophanol, Physcion, Hesperidin and Curcumin Modulate the Gene Expression of Pro-Inflammatory Mediators Induced by LPS in HepG2: In Silico and Molecular Studies

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 371 ◽  
Author(s):  
Selim ◽  
Elgazar ◽  
Abdel-Hamid ◽  
El-Magd ◽  
Yasri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Traditional Medicine ◽  
In Silico ◽  
Docking Study ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Molecular Docking Study ◽  
Necrosis Factor Alpha ◽  
In Silico Studies

Hepatitis is an inflammatory condition that can develop hepatocellular carcinoma. Traditional medicine has always been the pillar of medical practice. However, it became less compatible with the current understanding of the diseases and the possible treatment. Therefore, in silico tools could be utilized for building the bridge between the legacy of the past and the current medical approaches allowing access to new therapeutic discoveries. In this work, a Chinese traditional medicine database was screened using structure-based virtual screening to identify molecules that could inhibit p38 alpha mitogen-activated protein kinase (MAPK). Out of the identified compounds, four selected compounds: chrysophanol, physcion, curcumin and hesperidin were isolated from their respective sources and their structures were confirmed by spectroscopic methods. These compounds decreased the gene expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1beta (IL-1β) in lipopolysaccharide (LPS) induced inflammation in a hepatocellular carcinoma cell line (HepG2) in a dose-dependent manner. The molecular docking study revealed the specificity of these compounds towards p38 MAPK rather than other MAPKs. In conclusion, the molecular and in silico studies suggest that the isolated compounds could be a potential treatment for hepatitis by resolving inflammation controlled by MAPKs, thus limiting the development of further complications and lower side effects.

scholarly journals Natural products as anti-COVID-19 agents: An in silico study

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Chandan Sarkar ◽  
Sarmin Jamaddar ◽  
Milon Mondal ◽  
Abul Bashar Ripon Khalipha ◽  
Muhammad Torequl Islam ◽  
...  
Keyword(s):  
In Silico ◽  
Rna Virus ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Docking Study ◽  
Asiatic Acid ◽  
Molecular Docking Study ◽  
Viral Protease ◽  
In Silico Study ◽  
To Come

Background: The coronavirus disease 2019 (COVID-19) is a life threatening viral infection caused by a positivestrand RNA virus belonging to Coronaviridae family called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). This virus has infected millions of peoples, and caused hundreds of thousands of deaths around the world. Unfortunately, to date, there is no specific cure for SARS-CoV-2 infection, although researchers are working tirelessly to come up with a drug against this virus. Recently, the main viral protease has been discovered, and is regarded as an appropriate target for antiviral agents in the search for treatment of SARS-CoV-2 infection, due to its role in polyproteins processing during coronavirus replication. Methodology: This investigation (an in silico study) explores the effectiveness of 16 natural compounds from a literature survey against the protease of SARS-CoV-2 in an attempt to identify a promising antiviral agent through a molecular docking study. Results: Among the 16 compounds studied, apigenin, alpha-hederin, and asiatic acid exhibited significant docking performance and interacted with several amino acid residues of the main protease of SARS-CoV-2. Conclusion: In summary, apigenin, alpha-hederin, and asiatic acid protease inhibitors may be effective potential antiviral agents against the main viral protease (Mpro) to combat SARS-CoV-2.

scholarly journals Design and In Silico Study of the Novel Small Molecular MDM2 Inhibitors

2020 ◽  
Vol 11 (1) ◽  
pp. 8052-8064
Keyword(s):  
Protein Interaction ◽  
In Silico ◽  
P53 Protein ◽  
Docking Study ◽  
Rational Approach ◽  
The Novel ◽  
Molecular Docking Study ◽  
Protein Protein Interaction ◽  
In Silico Study ◽  
Cancer Agent

Protein-protein Interaction (PPIs) plays a central role in many diseased conditions. Therefore to target and to modulate PPIs is an efficient approach for the disease treatment. Cancer is also arising because of Protein-protein interaction. In cancer, the tumor suppressor p53 protein got inhibited by the MDM2 protein. p53 protein regulates the cell cycle and apoptosis. Interaction between the p53-MDM2 proteins is responsible for the inhibition of the p53 function. By this interaction, MDM2 degrades and inhibits the p53 protein. Hence, to target and inhibit the p53-MDM2 interaction for the treatment of cancer is the rational approach. By targeting this interaction with the drugs, we can selectively kill the cancer cells over the normal cells. Recently, p53-MDM2 interaction inhibitor drugs have been reported by many researchers and pharmaceutical companies. And several drugs entered into the clinical trials. In this study, a novel 1,2,4-triazole based molecules were designed as MDM2 inhibitors and performed their in-silico study. We designed the novel compound 01 and Lead 1a. In this work, In silico study of the Lead 1a and reference compounds (Nutlin 3a, RG7112) was carried out. The molecular docking study of the Novel 1,2,4-triazole based lead 1a and reference compounds was carried out. The docking score of the Lead 1a found to be better than Nutlin 3a and close to RG7112. The various possible conformations and binding affinity values were also determined by the docking study. These results indicate the Lead 1a as a potential MDM2 inhibitor and anti-cancer agent.

scholarly journals A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 184 ◽  
Author(s):  
Anca-Maria Borcea ◽  
Gabriel Marc ◽  
Ioana Ionuț ◽  
Dan C. Vodnar ◽  
Laurian Vlase ◽  
...  
Keyword(s):  
In Silico ◽  
Docking Study ◽  
Biological Evaluation ◽  
Antifungal Drugs ◽  
Biologically Active ◽  
Molecular Docking Study ◽  
Candida Spp ◽  
In Silico Admet ◽  
In Silico Studies

In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the binding poses towards lanosterol 14α-demethylase. An in silico ADMET analysis showed that the compounds possess drug-like properties and represent a biologically active framework that should be further optimized as potential hits.

scholarly journals In Silico studies of 4-Anilino Quinazoline derivatives as Anti-tubercular Agents

2020 ◽  
Vol 11 (4) ◽  
pp. 7468-7475
Author(s):  
Hemalatha K ◽  
Sujatha K ◽  
Panneerselvam P ◽  
Girija K
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Resistant Strain ◽  
In Silico ◽  
Research Work ◽  
Docking Study ◽  
Molecular Docking Study ◽  
In Silico Studies ◽  
Quinazoline Derivatives ◽  
Mycobacterial Cell Wall

Inh A, the Enoyl Acyl Carrier protein Reductase from Mycobacterium tuberculosis is one of the pivotal enzyme involved in the mycobacterial fatty acid elongation cycle and has been considered as an important target for anti-tubercular screening. Inhibition of Inh A affects the biosynthesis of the mycolic acids, which are the central constituents of the mycobacterial cell wall. In the present research work, 4-anilino quinazoline derivatives were designed based on the quinazoline based drugs by means of lipophilic insertion and Fragment replacement. The designed compounds were synthesized, and molecular docking studies were performed on the human pathogenic bacterial enzyme InhA from its parent domain Mycobacterium Tuberculosis. Molecular docking study revealed that compounds SMOQ2, SNAQ3, 4AAQ7, 2AP9, PABAQ10 were found to possess good binding affinity towards the target InhA. With reference to the binding energy obtained from molecular docking study, five compounds were subjected to in vitro anti-tubercular activity against M. tuberculosis  H37Rv and I2487 (Resistant strain) using BACTEC MGIT method. Compound SMOQ2 and 4AAQ7 showed sensitivity in both H37Rv (Sensitive strain) and I2487 (Resistant strain) at the concentration of 250, 500, 1000 and 1500 mcg/mL. In silico Pharmacokinetic predictions of the synthesized compounds were determined using SwissADME online web tool. All the synthesized compounds obeyed the Lipinski's rule of five properties.

scholarly journals Synthesis, Antibacterial Evaluation and in Silico Study of DOTA-fluoroquinolone Derivativessynthesis, Antibacterial Evaluation and in Silico Study of DOTA-fluoroquinolone Derivatives

2021 ◽  
Author(s):  
Weitian Li ◽  
Ge Hong ◽  
Lina Mao ◽  
Zengping Xu ◽  
Jiawen Wang ◽  
...  
Keyword(s):  
In Silico ◽  
Antimicrobial Activities ◽  
Water Soluble ◽  
Stable Complex ◽  
Molecular Docking Study ◽  
Topoisomerase Iv ◽  
Water Soluble Compound ◽  
In Silico Study ◽  
Low Toxicity ◽  
Antibacterial Evaluation

Abstract A series of water-soluble fluoroquinolones based upon DOTA modification were synthesized and characterized by NMR and HRMS spectra. All the newly prepared quinolones compounds exhibited potent antimicrobial activities against MRSA, P. aeruginosa and E. coli. Molecular docking study indicated they could form stable complex with DNA gyrase and topoisomerase IV-DNA respectively, ADMET prediction showed they were low toxicity to the mice as whole. Among them, water-soluble quinolone 4c exhibited promising antibacterial potency, its MIC, MBC value for MRSA and P. aeruginosa was (1.56, 6.25) µg/mL, (3.1, 12.5) µg/mL respectively. Atomic Force Microscope (AFM) imaging revealed 4c could effectively destroy MRSA bacterial membrane and wall, causing its contents to leak out. Cytotoxicity assay showed 4c had low toxicity to L-02, A549 and MCF-7, over 80% cell viability even at 100 µmol/L. These results showed that water-soluble compound 4c was a promising antibacterial candidate.

scholarly journals Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 342
Author(s):  
Ihsan A. Shehadi ◽  
Mohamad T. T. Abdelrahman ◽  
Mohamed Abdelraof ◽  
Huda R. M. Rashdan
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Trna Synthetase ◽  
Microbial Pathogens ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Silico Studies

A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (2) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Staphylococcus aureus, and Candida albicans. However, compounds 3 and 5 showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds 4 and 6, or only antifungal activity like compound 7. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS ) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound 3 showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (–8.4 and –9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound 3 is a good candidate for the next steps of the drug development process as an antimicrobial drug.

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