scholarly journals Insilico Design and Synthesis, Evaluation of Anti-Colon Cancer Activity of Novel Stilbene Hybrids

2021 ◽  
pp. 128-139
Author(s):  
Geethavani Meka ◽  
Yaswanth Murthaeti ◽  
Ramakrishna Chintakunta
Keyword(s):  
Colon Cancer ◽  
Binding Affinity ◽  
Acid Hydrazide ◽  
Docking Studies ◽  
Spectral Studies ◽  
Anticancer Activities ◽  
Mass Spectral ◽  
Design And Synthesis ◽  
Ic50 Value ◽  
Cancer Activity

Various biologically important Stilbene analogues were competently synthesized using inexpensive, non-toxic, and readily available amino acids and Stilbene; the systematic study was carried out to characterize parameters such as TLC, melting point, IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for anticancer activities. The molecular docking studies have been performed by using software Autodock 4.2, Autodock vina. The targeted proteins are P450a2 & Estrogen. The reaction of phenylacetic acid substituted Benzaldehyde, and triethylamine in acetic anhydride was irradiated in a microwave oven for 3 minutes at 700W afforded (2E)-3-(substituted phenyl)-2-phenylacrylic acid. The above compound, after irradiating with hydrazine provided (2E)-3-(substituted phenyl)-2-phenyl acrylic acid hydrazide. Anti-Cancer activity for synthesized compounds was evaluated using the MTT assay technique against colon cancer. The results were obtained as a percentage in cell lysis data. The IC50 value of the compounds was between 0.037-0.0257 µM/lt. Among all the compounds, tyrosine derivatives exhibited the more potent activity. Insilico studies PCB-arg having more binding affinity with the receptor Cytochrome P450 A2 and PCB-try having more binding affinity with the receptor estrogen beta when compared to other derivatives.

scholarly journals Anti-cancer and Antimicrobial Activity, In-Silico ADME and Docking Studies of Biphenyl Pyrazoline Derivatives

2020 ◽  
Vol 11 (1) ◽  
pp. 8266-8282
Keyword(s):  
Breast Cancer ◽  
Antimicrobial Activity ◽  
Binding Affinity ◽  
In Silico ◽  
Chemical Properties ◽  
Cancer Cell Line ◽  
Docking Studies ◽  
Spectral Studies ◽  
Compound 21 ◽  
Affinity Score

The present study deals with the multicomponent Michal addition reaction of xenyl chalcone (10-17) reacting with hydrazine hydrate in the presence of ethane carboxylic acid. It afforded new pyrazoline compounds. The propane pyrazoline derivatives (18-25) skeleton structure was confirmed by spectral studies like Fourier-Transform Infrared spectroscopy, 1H NMR, 13C NMR, and CHN analysis. The adsorption, distribution, metabolism, and excretion (ADME) properties of the synthesized molecules were investigated. The results obtained in-silico demonstrated that these molecules could be considered as orally active drug candidates due to their physical and chemical properties. The compounds (18-25) were subjected to docking prediction studies by protein (1UAG) and breast cancer protein (1OQA). While Comparing with the drug ciprofloxacin, among the series of eight compounds (18-25), compound 19, 20, and 24 have the best binding affinity score (-8.5 kcal/mol). We have selected only the compound 21 (4-Cl (electronegativity group)) compound for MTT assay of breast cancer cell line studies because it has the best binding affinity score in the binding study of the compound with 1OQA protein. Synthesized pyrazoline compound (18-25) also obeys the Lipinski rule of five and other criteria of drug-likeness properties. Among the synthesized pyrazoline compound (18-25), especially compound 21 (electronegativity group (4-Cl) has the best drug-likeness property and has a value of 7.16. Furthermore, antimicrobial activity of these compounds has been evaluated against five microbial strains, and from this result, some of the newly synthesized compounds exhibit good activity.

scholarly journals DESIGN AND SYNTHESIS OF NOVEL IMIDAZO[1,2-A]PYRIDINE DERIVATIVES AND THEIR ANTI-BACTERIAL ACTIVITY

2018 ◽  
Vol 11 (8) ◽  
pp. 252 ◽  
Author(s):  
Pushpalatha Budumuru ◽  
Srinivasarao Golagani ◽  
Venkata Siva Satyanaryana Kantamreddi
Keyword(s):  
Antibacterial Activity ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Beta Subunit ◽  
Diffusion Method ◽  
Pyridine Derivatives ◽  
Standard Drug ◽  
Mass Spectral ◽  
Design And Synthesis ◽  
Relationship Of

Objective: The present study aims to synthesize a novel derivatives of Imidazo[1,2-a]pyridines and the compounds were evaluated for their antibacterial activity.Methods: A series of newly synthesized compounds were characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, Fourier transform infrared, mass spectral analysis, and screened for their antibacterial activity by disc diffusion method. Molecular docking studies were performed with a bacterial beta subunit of DNA gyrase using Auto Dock 4.2.6, and the docked conformations were analyzed using visual molecular dynamics.Results: The structural activity relationship of the synthesized imidazo[1,2-a]pyridine derivatives was studied against Gram-positive and Gram-negative bacteria. Among the synthesized compounds N-benzyl-4-((2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl) acetamido)methyl) benzamide (9a) are possessing high activity against Bacillus subtilis. The zone of inhibition produced by the compound 9a is wider than that of remaining compounds used in this study.Conclusion: The synthesized compounds exhibited good antibacterial activity in comparison with standard drug streptomycin. This suggests that the compound 9a and its analogs are exerting their activity by probably inhibiting bacterial beta subunit of DNA gyrase.

scholarly journals Evaluation of in vitro antioxidant, anticancer activities and molecular docking studies of Capparis zeylanica Linn. leaves

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ruturaj A. Warake ◽  
Ravindra J. Jarag ◽  
Rakesh P. Dhavale ◽  
Rekha R. Jarag ◽  
Nikhil S. Lohar
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Leaf Extract ◽  
Docking Studies ◽  
Total Phenolic ◽  
Anticancer Activities ◽  
Her2 Protein ◽  
Molecular Docking Studies ◽  
Phenolic And Flavonoid

Abstract Background Capparis zeylanica Linn. leaf extract was subjected to phytochemical screening for the determination of antioxidant and anticancer activity on (MCF-7) human breast cancer cells. The phytoconstituents previously determined were subjected to molecular docking studies against human epidermal growth factor receptor 2 (HER2) protein as a target receptor to support antioxidant and anticancer activities. Results Powdered plant leaves were extracted by maceration method using ethyl acetate, chloroform, methanol, ethanol and distilled water. Preliminary phytochemical evaluation and total phenolic and flavonoid content of the extract were evaluated using biochemical tests. Total antioxidant capacity of the extract was evaluated using different assays. Anticancer potential of methanolic and ethanolic extracts was studied on human breast cancer cells. Molecular docking studies were performed to evaluate the binding interactions of phytoconstituents on HER2 protein using AutoDock Vina. Phytochemical evaluation confirmed the presence of saponins, flavonoids, tannins, phenols, carbohydrates and proteins. Ethanolic extract showed a maximum total phenolic and flavonoid content in support with antioxidant and anticancer activities. The ethanolic leaf extract showed 66.63% cell growth inhibition against MCF-7 cells. Molecular docking studies revealed the highest binding affinity (− 8.4 Kcal/mol) of α-amyrin followed by quercetin and β-carotene. Glucocapparin, syringic acid, vanillic acid and p-coumaric acid showed almost a similar binding affinity to the amino acid residues of HER2 protein as compared to 5-FU. Conclusion C. zeylanica leaf extract showed the presence of phenolic and flavonoid constituents responsible for antioxidant and in vitro anticancer activities. Molecular docking studies showed the binding affinity of phytoconstituents on targeted HER2 protein.

scholarly journals Chloropyridinyl Esters of Nonsteroidal Anti-Inflammatory Agents and Related Derivatives as Potent SARS-CoV-2 3CL Protease Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5782
Author(s):  
Arun K. Ghosh ◽  
Dana Shahabi ◽  
Monika Yadav ◽  
Satish Kovela ◽  
Brandon J. Anson ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
Covalent Bond ◽  
Gel Chromatography ◽  
Mass Spectral Analysis ◽  
Mass Spectral ◽  
Design And Synthesis ◽  
Protease Enzyme ◽  
Ic50 Value ◽  
3Cl Protease

We report the design and synthesis of a series of new 5-chloropyridinyl esters of salicylic acid, ibuprofen, indomethacin, and related aromatic carboxylic acids for evaluation against SARS-CoV-2 3CL protease enzyme. These ester derivatives were synthesized using EDC in the presence of DMAP to provide various esters in good to excellent yields. Compounds are stable and purified by silica gel chromatography and characterized using 1H-NMR, 13C-NMR, and mass spectral analysis. These synthetic derivatives were evaluated in our in vitro SARS-CoV-2 3CLpro inhibition assay using authentic SARS-CoV-2 3CLpro enzyme. Compounds were also evaluated in our in vitro antiviral assay using quantitative VeroE6 cell-based assay with RNAqPCR. A number of compounds exhibited potent SARS-CoV-2 3CLpro inhibitory activity and antiviral activity. Compound 9a was the most potent inhibitor, with an enzyme IC50 value of 160 nM. Compound 13b exhibited an enzyme IC50 value of 4.9 µM. However, it exhibited a potent antiviral EC50 value of 24 µM in VeroE6 cells. Remdesivir, an RdRp inhibitor, exhibited an antiviral EC50 value of 2.4 µM in the same assay. We assessed the mode of inhibition using mass spectral analysis which suggested the formation of a covalent bond with the enzyme. To obtain molecular insight, we have created a model of compound 9a bound to SARS-CoV-2 3CLpro in the active site.

Novel 7-substituted Fluoroquinolone Citrate Conjugates as Powerful Antibacterial and Anticancer Agents: Synthesis and Molecular Docking Studies

2019 ◽  
Vol 23 (18) ◽  
pp. 1992-2003
Author(s):  
Tejeswara R. Allaka ◽  
Jaya S. Anireddy
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Line ◽  
Anticancer Agents ◽  
Docking Studies ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Lipinski’S Rule ◽  
Ic50 Value ◽  
Pharmacokinetic Properties ◽  
Lipinski’S Rule Of Five

In this study, the synthesis and evaluation of norfloxacin analogues of dimethyl citrate conjugates were described and their antibacterial and anticancer activities were assessed. The cognate 7-substituted norfloxacin citrate conjugates are active against various strains of bacteria, including MRSA (methicillin-resistant Staphylococcus aureus) with higher activity than ciprofloxacin. Screening results indicated that compound 10 possessed good antibacterial activity against several microorganisms, with MIC values in the range of 0.16-0.35 mg/mL and MBCs in the range of 0.55-0.84 mg/mL. Experiments indicated that 9 demonstrated the most significant activity towards the HCT-15 cell line with IC50 value 8.2 ± 0.139 and against the HT-29 cell line with IC50 8.9 ± 0.122. The title compounds were also evaluated for determining the molecular and pharmacokinetic properties and drug-likeness model scores by using the Molinspiration-2008 and MolSoft-2007 softwares. The region isomeric conjugates followed the Lipinski’s rule of five can be considered as potential antibacterial and anticancer bioavailable oral leads. Compounds 9 and 10 possessed maximum drug-likeness scores. The docking pose interactions of target compounds with the active site of enzyme PDB: 2ZCS of Staphylococcus aureus were estimated by using Autodock 4.2, to calculate the affinity, binding orientation of the ligand with the target protein and to explore the finest conformations. The target compounds, 7, 8, 9, 10, with protein, were loaded separately into Auto dock tools (ADT) and evaluated. The citrate conjugates, 8, 9, showed better docking scores with amino acids Lys17, Ser21, Val268, Lys273 and Arg171, Arg265, Val268, Val273 with the binding energy -5.70, -5.57 kcal/mol and dissociation constant 66.62, 82.13 µM respectively.

DESIGN, SYNTHESIS, ANTIBACTERIAL AND ANTICANCER ACTIVITY OF 4-HYDROXY-3-(2-SUBSTITUTED-2-THIOXOETHYL)-1-PHENYL/ METHYLQUINOLIN-2(1H)-ONE DERIVATIVES

INDIAN DRUGS ◽  
2018 ◽  
Vol 55 (11) ◽  
pp. 32-39
Author(s):  
H. A Karmali ◽  
◽  
S. N. Mamle Desai ◽  
S. G. Shingade ◽  
M. B. Palkar ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Design Synthesis ◽  
Molegro Virtual Docker ◽  
Mass Spectral ◽  
Ic50 Value ◽  
Antibacterial And Anticancer Activity ◽  
Compound Ii ◽  
A549 Lung

A series of title compounds, 4-hydroxy-3-(2-substituted-2-thioxoethyl)-1-phenyl/methylquinolin-2(1H)- ones were synthesized and purity of the compounds was ascertained by TLC. The structures of the synthesized compounds were characterized by IR, NMR (1HNMR and 13CNMR) and mass spectral data. Molecular docking studies of the compounds were carried out using Molegro Virtual Docker. All the synthesized compounds were evaluated for anticancer activity against two different cell lines: K562 (leukemia) and A549 (lung cancer) and antibacterial evaluation was also carried out against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Compound (II-a1) showed MIC of 1 μg/mL against B. subtilis and 4 μg/mL against S. aureus. Compound ( II-b1) showed MIC of 4 μg/mL against B. subtilis and 2 μg/mL against S. aureus gram positive bacterial strains. Compound II-a2 showed anticancer activity with IC50 value = 0.765 μM/mL against K562 cell line (leukemia) and II-a3 with IC50 value = 0.774 μM/mL.

Design, Synthesis and Pharmacological Evaluation of New Thiazole Derivatives as Anthelmintic Agents

2020 ◽  
Vol 13 (5) ◽  
pp. 5075-5081
Author(s):  
Sirisha Kalam ◽  
Sai Krishn G ◽  
Kumara Swamy D ◽  
Sai Santhoshi K ◽  
Durga Prasad K
Keyword(s):  
Anthelmintic Activity ◽  
Docking Studies ◽  
Molecular Property ◽  
Thiazole Derivatives ◽  
Pharmacological Agents ◽  
Design Synthesis ◽  
Standard Drug ◽  
Lipinski’S Rule ◽  
Mass Spectral ◽  
Tubulin Protein

Pharmacological agents that kills parasites are essential drugs in some tropical countries. In this study, a series of 2-amino substituted 4-phenyl thiazole derivatives (4a-e) have been synthesized by the conventional method. The thiazole derivatives were synthesized by three steps. The obtained five derivatives were purified by recrystallization using methanol as a solvent or column chromatography. They were characterized by melting point, TLC, FTIR, 1H NMR and MASS spectral data. Compounds 4a-e were evaluated in silico by using different software’s (Lipinski’s Rule of 5, OSIRIS molecular property explorer, Molsoft molecular property explorer, and PASS & docking studies). These compounds were then evaluated for their possible anthelmintic activity against Indian adult earth worms (Pherituma postuma). All the compounds displayed significant anthelmintic activity. Compound 4c and 4e were more potent compounds when compared with the standard drug (mebendazole). Molecular docking studies guided and proved the biological activity against beta tubulin protein (1OJ0). In conclusions, these new molecules have promising potential as anthelmintic for treatment of parasites.   

Discovery of Some Antiviral Natural products to fight against Novel Corona Virus (SARS-CoV-2) using Insilico approach

2020 ◽  
Vol 23 ◽  
Author(s):  
Ashish Shah ◽  
Vaishali Patel ◽  
Bhumika Parmar
Keyword(s):  
Binding Affinity ◽  
Protein S ◽  
Docking Studies ◽  
Spike Protein ◽  
Enveloped Viruses ◽  
Bioactivity Prediction ◽  
Corona Virus ◽  
Main Protease ◽  
Antiviral Activities ◽  
Deadly Disease

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

A New Series Of 1,3-Dimethylxanthine Based Adenosine A2a Receptor Antagonists As A Non-Dopaminergic Treatment Of Parkinson’s Disease

2020 ◽  
Vol 17 ◽  
Author(s):  
Suman Rohilla ◽  
Ranju Bansal ◽  
Puneet Chauhan ◽  
Sonja Kachler ◽  
Karl-Norbert Klotz
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Studies ◽  
Binding Modes ◽  
Molecular Docking Studies ◽  
In Silico Docking ◽  
Adenosine A2a Receptor Antagonists ◽  
The Impact

Background: Adenosine receptors (AR) have emerged as competent and innovative nondopaminergic targets for the development of potential drug candidates and thus constitute an effective and safer treatment approach for Parkinson’s disease (PD). Xanthine derivatives are considered as potential candidates for the treatment Parkinson’s disease due to their potent A2A AR antagonistic properties. Objective: The objectives of the work are to study the impact of substituting N7-position of 8-m/pchloropropoxyphenylxanthine structure on in vitro binding affinity of compounds with various AR subtypes, in vivo antiparkinsonian activity and binding modes of newly synthesized xanthines with A2A AR in molecular docking studies. Methods: Several new 7-substituted 8-m/p-chloropropoxyphenylxanthine analogues have been prepared. Adenosine receptor binding assays were performed to study the binding interactions with various subtypes and perphenazine induced rat catatonia model was used for antiparkinsonian activity. Molecular docking studies were performed using Schrödinger molecular modeling interface. Results: 8-para-substituted xanthine 9b bearing an N7-propyl substituent displayed the highest affinity towards A2A AR (Ki = 0.75 µM) with moderate selectivity versus other AR subtypes. 7-Propargyl analogue 9d produced significantly longlasting antiparkinsonian effects and also produced potent and selective binding affinity towards A2A AR. In silico docking studies further highlighted the crucial structural components required to develop xanthine derived potential A2A AR ligands as antiparkinsonian agents. Conclusion: A new series of 7-substituted 8-m/p-chloropropoxyphenylxanthines having good affinity for A2A AR and potent antiparkinsonian activity has been developed.

Design and synthesis of new antifungals based on N- un-substituted azoles as 14α demethylase inhibitor

2020 ◽  
Vol 16 ◽  
Author(s):  
Asghar Davood ◽  
Aneseh Rahimi ◽  
Maryam Iman ◽  
Parisa Azerang ◽  
Soroush Sardari ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Antifungal Agents ◽  
Molecular Design ◽  
Pathogenic Fungi ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Receptor Interaction ◽  
Main Role ◽  
Design And Synthesis ◽  
Antifungal Antibiotics

Objective(s): Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). Nearly all azole antifungal agents are N-substituted azoles. In addition, an azolylphenalkyl pharmacophore is uniquely shared by all azole antifungals. Due to importance of nitrogen atom of azoles (N-3 of imidazole and N-4 of triazole) in coordination with heme in the binding site of the enzyme, here a group of N- un-substituted azoles in which both of nitrogen is un-substituted was reported. Materials and Methods: Designed compounds were synthesized by reaction of imidazole-4-carboxaldehyde with appropriate arylamines and subsequently reduced to desired amine derivatives. Antifungal activity against Candida albicans and Saccharomyces cervisiae were done using a broth micro-dilution assay. Docking studies were done using AutoDock. Results: Antimicrobial evaluation revealed that some of these compounds exhibited moderate antimicrobial activities against tested pathogenic fungi, wherein compound 3, 7 and 8 were potent. Docking studies propose that all of the prepared azoles interacted with 14α-DM, wherein azole-heme coordination play main role in drug-receptor interaction. Conclusion: Our results offer some useful references in order to molecular design performance or modification of this series of compounds as a lead compound to discover new and potent antimicrobial agents.

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