In Vitro and In Silico Studies of Glycyrrhetinic Acid Derivatives as Anti- Filarial Agents

2019 ◽  
Vol 19 (14) ◽  
pp. 1191-1200 ◽  
Author(s):  
Rekha Tyagi ◽  
Surjeet Verma ◽  
Shikha Mishra ◽  
Mrigank Srivastava ◽  
Sarfaraz Alam ◽  
...  
Keyword(s):  
Linear Chain ◽  
Qsar Model ◽  
Docking Studies ◽  
Glycyrrhetinic Acid ◽  
Standard Drug ◽  
Amide Derivatives ◽  
In Silico Studies ◽  
Parasite Motility ◽  
The Tropics

Background: Lymphatic filariasis is one of the chronic diseases in many parts of the tropics and sub-tropics of the world despite the use of standard drugs diethylcarbamazine and ivermectin because they kill microfilaries and not the adult parasites. Therefore, new leads with activity on adult parasites are highly desirable. Objective: Anti-filarial lead optimization by semi-synthetic modification of glycyrrhetinic acid (GA). Methods: The GA was first converted into 3-O-acyl derivative, which was further converted into 12 amide derivatives. All these derivatives were assessed for their antifilarial potential by parasite motility assay. The binding affinity of active GA derivatives on trehalose-6-phosphate phosphatase (Bm-TPP) was assessed by molecular docking studies. Results: Among 15 GA derivatives, GAD-2, GAD-3, and GAD-4 were found more potent than the GA and standard drug DEC. These derivatives reduced the motility of Brugia malayi adult worms by up to 74% while the GA and DEC reduced only up to 49%. Further, GA and most of its derivatives exhibited two times more reduction in MTT assay when compared to the standard drug DEC. These derivatives also showed 100% reduction of microfilariae and good interactions with Bm-TPP protein. Conclusion: The present study suggests that 3-O-acyl and linear chain amide derivatives of glycyrrhetinic acid may be potent leads against B. malayi microfilariae and adult worms. These results might be helpful in developing QSAR model for optimizing a new class of antifilarial lead from a very common, inexpensive, and non toxic natural product.

Synthesis, Antimicrobial Evaluation and In silico Studies of Novel 2,4- disubstituted-1,3-thiazole Derivatives

2018 ◽  
Vol 16 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Mir Mohammad Masood ◽  
Mohammad Irfan ◽  
Shadab Alam ◽  
Phool Hasan ◽  
Aarfa Queen ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Thiazole Derivatives ◽  
Standard Drug ◽  
Hek 293 ◽  
In Silico Studies

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). </P><P> Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 &#181;g/ml) against Candida tropicalis comparable to the standard drug, fluconazole (IC50 = 10.5 &#181;g/ml). Based on in vitro antimicrobial results, compounds 2f, 4c and 4e were selected for further pharmacological investigations. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed non-toxic nature of the selected compounds (2f, 4c and 4e). To ascertain their possible mode of action, docking studies with the lead inhibitors (2f, 4c and 4e) were performed using crystal structure coordinates of bacterial methionine aminopeptidases (MetAPs), an enzyme involved in bacterial protein synthesis and maturation. Results: The results of in vitro and in silico studies provide a rationale for selected compounds (2f, 4c and 4e) to be carried forward for further structural modifications and structure-activity relationship (SAR) studies against these bacterial infections. Conclusion: The study suggested binding with one or more key amino acid residues in the active site of Streptococcus pneumoniae MetAP (SpMetAP) and Escherichia coli MetAP (EcMetAP). In silico physicochemical properties using QikProp confirmed their drug likeliness.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

Elucidating the anti-biofilm and anti-quorum sensing potential of selenocystine against respiratory tract infections causing bacteria: in vitro and in silico studies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Bharti Patel ◽  
Subrata Mishra ◽  
Indira K. Priyadarsini ◽  
Sirisha L. Vavilala
Keyword(s):  
Quorum Sensing ◽  
Respiratory Tract ◽  
Protein Function ◽  
Docking Studies ◽  
Klebsiella Pneumonia ◽  
Potential Candidate ◽  
In Silico Studies ◽  
Specific Proteins ◽  
Tract Infections

Abstract Bacteria are increasingly relying on biofilms to develop resistance to antibiotics thereby resulting in their failure in treating many infections. In spite of continuous research on many synthetic and natural compounds, ideal anti-biofilm molecule is still not found thereby warranting search for new class of molecules. The current study focuses on exploring anti-biofilm potential of selenocystine against respiratory tract infection (RTI)-causing bacteria. Anti-bacterial and anti-biofilm assays demonstrated that selenocystine inhibits the growth of bacteria in their planktonic state, and formation of biofilms while eradicating preformed-biofilm effectively. Selenocystine at a MIC50 as low as 42 and 28 μg/mL effectively inhibited the growth of Klebsiella pneumonia and Pseudomonas aeruginosa. The antibacterial effect is further reconfirmed by agar cup diffusion assay and growth-kill assay. Selenocystine showed 30–60% inhibition of biofilm formation in K. pneumonia, and 44–70% in P. aeruginosa respectively. It also distorted the preformed-biofilms by degrading the eDNA component of the Extracellular Polymeric Substance matrix. Molecular docking studies of selenocystine with quorum sensing specific proteins clearly showed that through the carboxylic acid moiety it interacts and inhibits the protein function, thereby confirming its anti-biofilm potential. With further validation selenocystine can be explored as a potential candidate for the treatment of RTIs.

scholarly journals QSAR, molecular docking studies, ligand-based design and pharmacokinetic analysis on Maternal Embryonic Leucine Zipper Kinase (MELK) inhibitors as potential anti-triple-negative breast cancer (MDA-MB-231 cell line) drug compounds

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Hadiza Abdulrahman Lawal ◽  
Adamu Uzairu ◽  
Sani Uba
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Triple Negative Breast Cancer ◽  
Leucine Zipper ◽  
Triple Negative ◽  
Qsar Model ◽  
Docking Studies ◽  
Model Parameters ◽  
Standard Drug ◽  
Molecular Docking Studies

Abstract Background Cancer of the breast is known to be among the top spreading diseases on the globe. Triple-negative breast cancer is painstaking the most destructive type of mammary tumor because it spreads faster to other parts of the body, with high chances of early relapse and mortality. This research would aim at utilizing computational methods like quantitative structure–activity relationship (QSAR), performing molecular docking studies and again to further design new effective molecules using the QSAR model parameters and to analyze the pharmacokinetics “drug-likeliness” properties of the new compounds before they could proceed to pre-clinical trials. Results The QSAR model of the derivatives was highly robust as it also conforms to the least minimum requirement for QSAR model from the statistical assessments of (R2) = 0.6715, (R2adj) = 0.61920, (Q2) = 0.5460 and (R2pred) of 0.5304, and the model parameters (AATS6i and VR1_Dze) were used in designing new derivative compounds with higher potency. The molecular docking studies between the derivative compounds and Maternal Embryonic Leucine Zipper Kinase (MELK) protein target revealed that ligand 2, 9 and 17 had the highest binding affinities of − 9.3, − 9.3 and − 8.9 kcal/mol which was found to be higher than the standard drug adriamycin with − 7.8 kcal/mol. The pharmacokinetics analysis carried out on the newly designed compounds revealed that all the compounds passed the drug-likeness test and also the Lipinski rule of five. Conclusions The results obtained from the QSAR mathematical model of parthenolide derivatives were used in designing new derivatives compounds that were more effective and potent. The molecular docking result of parthenolide derivatives showed that compounds 2, 9 and 17 had higher docking scores than the standard drug adriamycin. The compounds would serve as the most promising inhibitors (MELK). Furthermore, the pharmacokinetics analysis carried out on the newly designed compounds revealed that all the compounds passed the drug-likeness test (ADME and other physicochemical properties) and they also adhered to the Lipinski rule of five. This gives a great breakthrough in medicine in finding the cure to triple-negative breast cancer (MBA-MD-231 cell line).

Antimicrobial Screening, in Silico Studies and QSAR of Chalcone-based 1,4-disubstituted 1,2,3-triazole Hybrids

Drug Research ◽  
2020 ◽  
Author(s):  
Pinki Yadav ◽  
Kashmiri Lal ◽  
Ashwani Kumar
Keyword(s):  
Topoisomerase Ii ◽  
Antimicrobial Properties ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Binding Modes ◽  
E Coli ◽  
Structure Activity ◽  
In Silico Studies ◽  
Microbial Strains

AbstractThe in vitro antimicrobial properties of some chalcones (1a–1c ) and chalcone tethred 1,4-disubstituted 1,2,3-triazoles (2a–2u) towards different microbial strains viz. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans are reported. Compounds 2g and 2u exhibited better potency than the standard Fluconazole with MIC values of 0.0063 µmol/mL and 0.0068 µmol/mL, respectively. Furthermore, molecular docking was performed to investigate the binding modes of two potent compounds 2q and 2g with E. coli topoisomerase II DNA gyrase B and C. albicans lanosterol 14α-demethylase, respectively. Based on these results, a statistically significant quantitative structure activity relationship (QSAR) model was successfully summarized for antibacterial activity against B. subtilis.

scholarly journals Synthesis, in vitro and in silico Studies of Naphthalene Pyrazoline Prop-2-en-1-one Derivatives

2020 ◽  
Vol 32 (8) ◽  
pp. 1849-1856
Author(s):  
B. Prabha ◽  
C. Raja ◽  
S. Nathiya ◽  
M.R. Ezhilarasi
Keyword(s):  
Binding Affinity ◽  
Addition Reaction ◽  
Condensation Reaction ◽  
Docking Studies ◽  
High Drug ◽  
In Silico Studies ◽  
Drug Score ◽  
The Michael Addition ◽  
High Inhibition

The synthesized new naphthalene pyrazoline prop-2-en-1-one derivatives (NDPP 1-8) were obtained by the Michael addition reaction of ethyl propanoate, hydrazine hydrate with NPD as a multicomponent scaffold. (E)-1-(naphthalen-3-yl)-3-phenylprop-2-en-1-one (NPD) was formed from 2-acetyl naphthalene and substituted aldehyde via Claisen-Schmidt condensation reaction. The NDPP skeleton structures were confirmed by infrared, 1H & 13C NMR spectral data and elemental analysis. The structure of NDPP compounds was subjected to molecular docking and ADME studies. The result of ADME prediction, compound NDPP 2, which contains electron withdrawing -Cl group has high drug-likeness value 4.21 than the compounds NDPP 4 and 7 which had electron donating CH3 and OCH3 group shows the drug-likeness value 2.62. The NDPP 2 also has high drug score 0.63 than NDPP 4 and NDPP 7 have drug score 0.60 and 0.69, respectively. Docking studies shows that compound NDPP 5 which also contain electron withdrawing NO2 group has good binding affinity value -8.8 Kcal/mol were docked with 1UAG protein. These compounds showed good drug-likeness value 2.25 and drug score 0.65. in vitro Studies have a high inhibition value for the same NO2 substituted derivative. All the compounds have higher binding affinity value than standards binding affinity value.

scholarly journals Structure-Antifouling Activity Relationship and Molecular Targets of Bio-Inspired(thio)xanthones

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1126 ◽  
Author(s):  
Joana R. Almeida ◽  
Andreia Palmeira ◽  
Alexandre Campos ◽  
Isabel Cunha ◽  
Micaela Freitas ◽  
...  
Keyword(s):  
Acetylcholinesterase Activity ◽  
Qsar Model ◽  
Artemia Salina ◽  
Activity Relationship ◽  
Predictive Capacity ◽  
Antifouling Activity ◽  
In Silico Studies ◽  
Mussel Adhesive

The development of alternative ecological and effective antifouling technologies is still challenging. Synthesis of nature-inspired compounds has been exploited, given the potential to assure commercial supplies of potential ecofriendly antifouling agents. In this direction, the antifouling activity of a series of nineteen synthetic small molecules, with chemical similarities with natural products, were exploited in this work. Six (4, 5, 7, 10, 15 and 17) of the tested xanthones showed in vivo activity toward the settlement of Mytilus galloprovincialis larvae (EC50: 3.53–28.60 µM) and low toxicity to this macrofouling species (LC50 > 500 µM and LC50/EC50: 17.42–141.64), and two of them (7 and 10) showed no general marine ecotoxicity (<10% of Artemia salina mortality) after 48 h of exposure. Regarding the mechanism of action in mussel larvae, the best performance compounds 4 and 5 might be acting by the inhibition of acetylcholinesterase activity (in vitro and in silico studies), while 7 and 10 showed specific targets (proteomic studies) directly related with the mussel adhesive structure (byssal threads), given by the alterations in the expression of Mytilus collagen proteins (PreCols) and proximal thread proteins (TMPs). A quantitative structure-activity relationship (QSAR) model was built with predictive capacity to enable speeding the design of new potential active compounds.

scholarly journals Design, Synthesis and Pharmacological Evaluation of Novel Imidazopyridine Analogues as Proton Pump Antagonist

2020 ◽  
Vol 32 (4) ◽  
pp. 776-782
Author(s):  
Ravindra S. Sonawane ◽  
Kiran D. Patil ◽  
Avinash V. Patil
Keyword(s):  
Spectral Analysis ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Docking Studies ◽  
Design Synthesis ◽  
Standard Drug ◽  
Imidazopyridine Derivatives

A series of novel imidazopyridine derivatives as proton pump inhibitors was designed with compounds of CID data base and explored considering AZD0865 as standard. Many compounds were identified and docked in proton pump ATPase pocket (PDB ID: 4ux2). Molecular docking studies revealed that many compounds showed good proton pump ATPase inhibitory activity. The docking poses revealed the interaction of ligands with amino acid. The standard drug AZD0865 had docking score of -7.112302 and displayed interactions with Asn138 and Asp137. A series of novel imidazopyridine derivatives as proton pump inhibitors were docked, synthesized and characterized by IR, NMR, CHN and MS spectral analysis. The target imidazopyridines were prepared from substituted 2-aminonicotinic acid and 2-bromo-1-substituted ethanone. in vitro Studies explained that few compounds exhibited moderate to good proton pump ATPase inhibitory activity in comparison with the reference drugs i.e. AZD0865. Compounds 11 and 12 shown higher activities with the IC50 4.3. Compounds 1, 4, 6, 7, 8, 10 and 13 showed weak anti-ulcer activity with its IC50 5.2, 5.8, 5.5, 5.1, 4.9, 4.6 and 5.9 and positive control AZD0865 shown IC50 2.0.

scholarly journals Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies

2020 ◽  
Author(s):  
Mohsinul Mulk Bacha ◽  
Humaira Nadeem ◽  
Shafiq Ur Rehman ◽  
Sadia Sarwar ◽  
Aqeel Imran ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Molecular Docking ◽  
Aldose Reductase ◽  
Diabetic Complications ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Aldehyde Reductase ◽  
Standard Drug ◽  
Molecular Docking Studies

Abstract In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2.

scholarly journals Synthesis, Spectral Characterization, in Vitro and in Silico Studies of Benzodioxin Pyrazoline derivatives

2020 ◽  
Vol 11 (2) ◽  
pp. 9126-9138
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Oral Absorption ◽  
Docking Studies ◽  
In Vitro Studies ◽  
Bacterial Protein ◽  
Online Tools ◽  
In Silico Studies ◽  
Theoretical Results

The present study deals with the in silico and in vitro studies of DBDP derivatives, which is formed from the Michal-addition reaction of DihydroBenzo[b]Dioxin Chalcone Derivatives(DBDD) with hydrazine hydrate and carboxyethane. The DBDD were synthesized via Claisen condensation between substituted aldehyde and 1,4-(benzodioxan-6-yl)-methyl ketone. The newly arrived compounds were characterized by IR and NMR spectra. The structurally confirmed synthesized compounds were screened against 1UAG microbial protein, 1OQA cancer protein using auto dock software, and ADME properties also found by using (in silico) Swissadme and Molinspiration online tools. All the newly arrived DBDP compounds have passed the acceptable values of ADME (drug-likeness), medicinal property, and lead likeness in ADME prediction. Compound DBDP-9 scored better values in drug-likeness. It obeys the five basic rules (Lipinski, Ghose, Verber, Egan, and Muegge) of medicinal chemistry property, passed the PAINS, Brenk filters with 0 violation, and also have better lead likeness value. All the other compounds in this series also passed the above-mentioned properties with 1 or 2 violations only present in PAINS and Brenk filter. This theoretical results incitement to performed docking and in vitro studies of the DBDP derivatives. Docking studies results that the good I.S averse to 1 UAG bacterial protein than standard drugs and also give impact values in the docking against 1OQA breast cancer protein. Overall observation from the above studies, DBDP-9 has a maximum oral absorption value 91.36% with 0 violation alert in drug-likeness, medicinal property, and pharmacokinetics filter. DBDP-4 has a good I.S (-8.8), DBDP-2 has 4 numbers of HBI as standard, and all the DBDP 1-9 compounds have higher I.S than the standard and also have impact I.S against 1OQA breast cancer protein.

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