scholarly journals Synthesis of novel ketene dithioacetals via one pot reaction: Molecular modelling in-silico Admet studies and antimicrobial activity

2021 ◽  
pp. 187-202
Author(s):  
Mohammad Arif Pasha ◽  
Sumanta Mondal ◽  
Naresh Panigrahi
Keyword(s):  
In Silico ◽  
Binding Energies ◽  
Inhibition Mechanism ◽  
Good Prediction ◽  
One Pot ◽  
Ketene Dithioacetals ◽  
In Silico Admet ◽  
In Silico Studies ◽  
Three Component Reaction

A simple and efficient method for the synthesis of fifteen novel ketene dithioacetals (2-(6-amino5-cyano-4-aryl-4H-1,3-dithiin-2-ylidene) malononitrile) via a one-pot three-component reaction of activated methylene group malononitrile with carbon disulfide in the presence of arylidene malononitriles were reported. The effects of LiOH.H2O as a base at different concentrations have been investigated and can provide products in good yields at 40-50ºC temperature (54-89%). All the synthesized ketene dithioacetals compounds (MCB1-MCB15) were checked for favorable pharmacokinetic param¬eters along with toxicities which are based on drug-likeness explained by Lipinski’s rule of five by Med chem designer software correlated with that of pkCSM online tool. Explorations of synthesized ketene dithioacetals compounds for the antimicrobial study were found to be effective towards Staphylococcus aureus (MCB5 and MCB13) with a zone of inhibition at 26mm and 22mm which is compared to that of standard ciprofloxacin (26mm). This made our study to explore the inhibition mechanism with the help of molecular docking studies with possible binding energies (-6.4 to -8.9 kJ/mol) by pyrx 0.8 software to represent a good prediction of interactions between the ligand and protein (2XCT). Further evaluation of druggability and ADMET predictions compounds MCB5 and MCB13 were found to be effective. Based on the in-vitro and in-silico studies a series of ketene dithioacetals compounds may be helpful for further studying SAR and designing more potent antimicrobials.

scholarly journals In Silico Drug Discovery of 4-Hyroxypanduratin A, 6-Gingerol and Luteolin Targeting Nipah Virus

2021 ◽  
pp. 477-484
Author(s):  
Anurag Verma ◽  
Piyush Mittal ◽  
Milind S. Pande ◽  
Neelanchal Trivedi
Keyword(s):  
Fusion Protein ◽  
In Silico ◽  
Virus Entry ◽  
Nipah Virus ◽  
Binding Energies ◽  
Viral Agent ◽  
In Silico Studies ◽  
Viral Target ◽  
Dietary Food

Nipah Virus is a zoo tonic virus and has re-emerged again with more deadliness. NiV has infected many animals and humans worldwide and a huge loss to life has been faced. NiV contains a Fusion protein on its outer membrane which helps in the virus entry into the host cell. This fusion protein is a virulent factor and is a major anti-viral target. Many medicinal plants have been used against viral diseases, current research aims towards the potential of three daily dietary food elements that can be used as an anti-viral agent. In-silico studies are performed with 4-hyroxypanduratin A, 6-gingerol and Luteolin against the NiV-F and binding energies were calculated. It was reported that these phyto-compounds have good negative binding energies and they have the promising potential against Nipah Virus. Further in-vitro research can be performed with these phyto-compounds to design a specific drug against Nipah Virus.

The Inhibitory Effect of Three Essential Oils on Candida rugosa Lipase: In Vitro and In Silico Studies

2020 ◽  
Vol 10 (3) ◽  
pp. 208-215 ◽  
Author(s):  
Talia Serseg ◽  
Khedidja Benarous ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Essential Oils ◽  
In Silico ◽  
Candida Rugosa ◽  
Inhibitory Effect ◽  
Mentha Piperita ◽  
Inhibition Mechanism ◽  
Syzygium Aromaticum ◽  
In Silico Studies

Background: Essential oils have been used for centuries. EOs are gaining increasing interest because of their acceptance by consumers and their safe status. For the first time, the effect of essential oils on the inhibition of lipases has been investigated in this work. Objective: We aimed in this study to investigate in vitro the inhibitory effects of the three essential oils of most used spices: Peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum L.) and Cloves (Syzygium aromaticum L. Merr. et Perry) against Candida rugose lipase. In silico studies using molecular docking have been achieved to study the inhibition mechanism of major compounds of EO: menthol, carvacrol, eugenol and cinnamylaldehyde toward CRL. Methods: The inhibitory effect of three essential oils were determined by candida rugosa enzyme and pNP-L as substrate using spectrophotometry. Autodock vina was used for molecular docking with 50 runs. Results: We have found that these essential oils have a strong inhibitory effect with IC50 values 1.09, 1.78 and 1.13 mg/ml compared with Orlistat 0.06 mg/ml. The results show competitive inhibition for the three major compounds Menthol, Carvacrol and Eugenol with uncompetitive inhibition for Cinnamaldehyde. Different repetition ratios of hydrogen bonds and hydrophobic interactions were observed. The saved interactions were with His449, Ser209, Gly123, Gly124 and Phe344 for all molecules. Conclusion: These observations support using and considering essential oils and their major compounds as good sources for design new drugs to treat candidiasis and other diseases related to Lipases.

scholarly journals In-vitro anti-diabetic activity and in-silico studies of binding energies of palmatine with alpha-amylase, alpha-glucosidase and DPP-IV enzymes

Pharmacia ◽  
2020 ◽  
Vol 67 (4) ◽  
pp. 363-371
Author(s):  
Patrick Okechukwu ◽  
Mridula Sharma ◽  
Wen Hui Tan ◽  
Hor Kuan Chan ◽  
Kavita Chirara ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Energies ◽  
Alpha Amylase ◽  
Binding Interactions ◽  
Inhibiting Effect ◽  
Dpp Iv ◽  
In Silico Studies ◽  
Significant Difference ◽  
Alpha Glucosidase

Palmatine a protoberberine alkaloid has been previously reported to possess in vivo antidiabetic and antioxidant property. The aim of the experiment is to evaluate the in vitro antidiabetic activity and in-silico studies of the binding energies of Palmatine, acarbose, and Sitagliptin with the three enzymes of alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase-IV (DPP-IV). The in vitro antidiabetic study was done by evaluating the inhibitory effect of palmatine on the activities of alpha-amylase, alpha-glucosidase, and DPP-IV. Acarbose, and sitagliptin was used as standard drug. The molecular docking study was performed to study the binding interactions of palmatine with alpha-glucosidase, a-amylase, and DPP-IV. The binding interactions were compared with the standard compounds Sitagliptin and acarbose. Palmatine with IC50 (1.31 ± 0.27 µM) showed significant difference of (< 0.0001) higher inhibiting effect on alpha-amylase and weak inhibiting effect on alpha-glucosidase enzyme with IC50 (9.39 ± 0.27 µM) and DPP-IV with IC50 (8.7 ± 1.82 µM). Palmatine possess inhibition effect on the three enzymes.

scholarly journals Facile One-Pot Multicomponent Synthesis of Pyrazolo-Thiazole Substituted Pyridines with Potential Anti-Proliferative Activity: Synthesis, In Vitro and In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3103
Author(s):  
Islam H. El El Azab ◽  
Rania B. Bakr ◽  
Nadia A. A. Elkanzi
Keyword(s):  
Cell Lines ◽  
In Silico ◽  
Topoisomerase Ii ◽  
Human Cancer ◽  
Docking Simulation ◽  
Cytotoxic Potential ◽  
One Pot ◽  
In Silico Docking ◽  
In Silico Studies

Pyrazolothiazole-substituted pyridine conjugates are an important class of heterocyclic compounds with an extensive variety of potential applications in the medicinal and pharmacological arenas. Therefore, herein, we describe an efficient and facile approach for the synthesis of novel pyrazolo-thiazolo-pyridine conjugate 4, via multicomponent condensation. The latter compound was utilized as a base for the synthesis of two series of 15 novel pyrazolothiazole-based pyridine conjugates (5–16). The newly synthesized compounds were fully characterized using several spectroscopic methods (IR, NMR and MS) and elemental analyses. The anti-proliferative impact of the new synthesized compounds 5–13 and 16 was in vitro appraised towards three human cancer cell lines: human cervix (HeLa), human lung (NCI-H460) and human prostate (PC-3). Our outcomes regarding the anti-proliferative activities disclosed that all the tested compounds exhibited cytotoxic potential towards all the tested cell lines with IC50 = 17.50–61.05 µM, especially the naphthyridine derivative 7, which exhibited the most cytotoxic potential towards the tested cell lines (IC50 = 14.62–17.50 µM) compared with the etoposide (IC50 = 13.34–17.15 µM). Moreover, an in silico docking simulation study was performed on the newly prepared compounds within topoisomerase II (3QX3), to suggest the binding mode of these compounds as anticancer candidates. The in silico docking results indicate that compound 7 was a promising lead anticancer compound which possesses high binding affinity toward topoisomerase II (3QX3) protein.

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.

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Di-hydropyridine Analogs as Potent Antioxidants

2019 ◽  
Vol 19 (29) ◽  
pp. 2676-2686 ◽  
Author(s):  
Saddala Madhu Sudhana ◽  
Pradeepkiran Jangampalli Adi
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Metal Chelating ◽  
In Silico Admet ◽  
Dpph Method

Aims: The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5- methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. Background: An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine, 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (amlodipine) 1 were chemical synthesized process. Materials & Methods: In this process, various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction with 1 in the presence of N,N–dimethylpiperazine as a base in THF at 50-550 oC, the corresponding title compounds 3(a-e) and 5(a-e) in high yields. Furthermore, the compounds 3(a-e) and 5(a-e) were evaluated for antioxidant activity (DPPH method), metal chelating activity, hemolytic activity, antioxidant assay (ABTS method), cytotoxicity, molecular docking and in silico ADMET properties. Result: Results revealed that 5a, 5e, 3d, 3a and 5c exhibited high antioxidant, metal chelating activities, but 5a, 5e and 3d exhibited low activity. The molecular docking studies and ADMET of suggested ligands showed the best binding energies and non-toxic properties. Conclusion: The present in silico and in vitro evaluations suggested that these dihydropyridine derivatives act as potent antioxidants and chelating agents which may be useful in treating metals induced oxidative stress associated diseases.

2-Oxo-1,2,3,4-tetrahydropyrimidines Ethyl Esters as Potent β- Glucuronidase Inhibitors: One-pot Synthesis, In vitro and In silico Studies

2018 ◽  
Vol 14 (8) ◽  
pp. 818-830 ◽  
Author(s):  
Sarosh Iqbal ◽  
Nimra N. Shaikh ◽  
Khalid M. Khan ◽  
Sehrish Naz ◽  
Zaheer Ul-Haq ◽  
...  
Keyword(s):  
In Silico ◽  
Ethyl Esters ◽  
One Pot ◽  
One Pot Synthesis ◽  
In Silico Studies

In vitro and in silico studies of two 1,4-naphthoquinones and their topical formulation in bigels

2021 ◽  
Vol 18 ◽  
Author(s):  
Imen Khelifi ◽  
Audrey Tourrette ◽  
Daycem Khelifi ◽  
Thomas Efferth ◽  
El Akrem Hayouni ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Water Solubility ◽  
Biological Activities ◽  
Binding Energies ◽  
Topical Formulation ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
In Silico Studies

Background: 1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving the diffusion and bioavailability of NQs into the skin. Objective: We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application. Methods: Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as a non-polar solvent and span 65 as organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a “Franz cell” in vitro permeation model. Results: Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds to LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC50: 2.6 and 9.8 µM) y. The M1 release from bigels was faster and more efficient than that of M2. Conclusion: M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.

scholarly journals Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations and Pharmacokinetic Predictions of Some Methyl β-d-Galactopyranoside Analogs

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7016
Author(s):  
Md. Ruhul Amin ◽  
Farhana Yasmin ◽  
Mohammed Anowar Hosen ◽  
Sujan Dey ◽  
Shafi Mahmud ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Density Functional ◽  
Dynamics Simulation ◽  
Dynamic Simulations ◽  
Stable Conformation ◽  
Chemical Structures ◽  
In Silico Admet ◽  
In Silico Studies

A series of methyl β-D-galactopyranoside (MGP, 1) analogs were selectively acylated with cinnamoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to yield 6-O-substitution products, which were subsequently converted into 2,3,4-tri-O-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (4, 5, 6, and 9) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich’s ascites carcinoma (EAC) cells with an IC50 value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties, whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In silico ADMET study suggested all the designed molecules to be noncarcinogenic, with low aquatic and nonaquatic toxicity. In summary, all of these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.

In-silico studies and wet lab validation of Camptothecin derivatives for anti-cancer activity against liver (HepG2) and lung (A549) cancer cell lines

2021 ◽  
Vol 21 ◽  
Author(s):  
Komal Kalani ◽  
Dharmendra Kumar Yadav ◽  
Sarfaraz Alam ◽  
Feroz Khan ◽  
Mahendra P. Kashyap ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cell ◽  
In Silico ◽  
Topoisomerase I ◽  
Cancer Cell Lines ◽  
In Silico Admet ◽  
In Silico Studies

Bcakground: In the present study we have explored the utility of QSAR modelling, in silico ADMET, docking, chemical semi-synthesis and in vitro evaluation studies for the identification of active camptothecin (CPT) derivatives against cancer targeting human liver (HepG2) and lung (A549) cancer cell lines. Methods: Two QSAR models were developed as screenings tools using multiple linear regression (MLR) method followed by ADMET and docking studies. The regression coefficient (r2) and cross-validation regression coefficients (rCV2T) of the QSAR model for HepG2 cell line was 0.95 and 0.90 respectively, and for A549 cell line it was 0.93 and 0.81, respectively. Results: In silico studies show that CPT derivatives (CPT-1 and CPT-6) possess drug-like properties. Docking performed on DNA Topoisomerase-I, showed significant binding affinity. Finally, predicted active derivatives were chemically semi synthesized, spectroscopically characterized and evaluated in-vitro for cytotoxic/anticancer activity against HepG2 and A549 cell lines. Conclusion: The experimental results agreed with the predicted results. These findings may be of immense importance in the anticancer drug development from an inexpensive and widely available natural product, camptothecin.

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