scholarly journals Structural optimization of 4-(imidazol-5-yl)pyridine derivatives affords broad-spectrum anticancer agents with selective B-RAFV600E/p38α kinase inhibitory activity: Synthesis, in vitro assays and in silico study

2022 ◽  
pp. 106115
Author(s):  
Eslam M.H. Ali ◽  
Karim I. Mersal ◽  
Usama M. Ammar ◽  
Seyed-Omar Zaraei ◽  
Mohammed S. Abdel-Maksoud ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Anticancer Agents ◽  
Inhibitory Activity ◽  
In Silico ◽  
In Vitro Assays ◽  
Pyridine Derivatives ◽  
In Silico Study ◽  
Kinase Inhibitory Activity ◽  
P38α Kinase

Repurposing of auranofin against bacterial infections: An In silico and In vitro study

2020 ◽  
Vol 16 ◽  
Author(s):  
Nidhi Sharma ◽  
Arti Singh ◽  
Ruchika Sharma ◽  
Anoop Kumar
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Antibacterial Agent ◽  
Bacterial Infections ◽  
In Vitro Assays ◽  
Infection Model ◽  
Synergistic Activity ◽  
Bacterial Strains ◽  
Molecular Docking Study

Aim: The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent. Methods: In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software). Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate multimodal mechanism of action of auranofin. Finally, MTT assay has shown non-cytotoxic effect of auranofin. Conclusion: In conclusion, auranofin in combination with existing antibiotics could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides possibility of use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.

Natural chemical entities as bioactive moiety from weaver ant, Oecophylla smaragdina: An in vitro and in silico Study

2020 ◽  
Vol 17 ◽  
Author(s):  
Suchismeeta Behera ◽  
Priyanka Dash ◽  
Amulyaratna Behera ◽  
Chinmaya Chidananda Behera ◽  
Prafulla Kumar Mohanty
Keyword(s):  
Methyl Ester ◽  
Inhibitory Activity ◽  
In Silico ◽  
Acid Methyl Ester ◽  
Hexane Extract ◽  
Bioactive Molecules ◽  
Hexadecanoic Acid ◽  
Acid Methyl ◽  
In Silico Study

Background: Since time immemorial the ethnic community of Mayrubhanj District, Odisha, India has preferred to Olecophylla smaragdina as traditional medicine for their multiple ailments. Hence, the objective of the investigation is to scientifically examine the myth behind ethno-zoological claims using chemometric analysis as well as in vitro and in silico study. Methods: The maceration method was used for the extraction of O. smaragdina using hexane and methanol. In this study, various bioactive compounds of O. smaragdina were identified through GC MS analysis followed by an antimicrobial activity. The species was further studied for their binding modes for in silico inhibition of a choice of bacterial proteins using Biovia Discovery studio software. Results: Tetradecanoic acid, hexadecanoic acid, methyl ester, hexadecenoic acid, n-hexadecanoic acid, 9-octadecenoic acid, methyl ester, oleic acid, 9-octadecenamide are some important bioactive constituents identified through GCMS analysis. The hexane extract was found to be maximum inhibitory activity against Staphyllococus aureus. The % inhibitory activity of hexane and methanolic extract against S. aureus at a concentration of 400 μg/mL was found to be 90 and 83%, respectively. The high inhibitory capacity of the n-hexane extract was comparable to the standard drug Gentamycin which further supported the high receptor binding affinity of identified compound Octadecanoic acid towards Tyrosol-t RNA synthetase of staphylococcus aureus (PDB ID: 1JIK). Conclusion: Interestingly, this is probably the first report that the obtained bioactive molecules from O. smaragdina showed that binding site identification to carry out molecular docking studies and results showed that the better affinity to bind with suitable targeted moiety.

scholarly journals Cinnamaldehyde, cinnamic acid, and cinnamyl alcohol, the bioactives of Cinnamomum cassia exhibit HDAC8 inhibitory activity: An In vitro and In silico study

2017 ◽  
Vol 13 (51) ◽  
pp. 645 ◽  
Author(s):  
Ruchika Kaul-Ghanekar ◽  
Mangesh Patil ◽  
AmitS Choudhari ◽  
Savita Pandita ◽  
Md Ataul Islam ◽  
...  
Keyword(s):  
Cinnamic Acid ◽  
Inhibitory Activity ◽  
In Silico ◽  
Cinnamyl Alcohol ◽  
Cinnamomum Cassia ◽  
In Silico Study

Design, synthesis and evaluation of potential inhibitors for poly(ADP-ribose) polymerase members 1 and 14

2020 ◽  
Vol 12 (24) ◽  
pp. 2179-2190
Author(s):  
Caleb M Kam ◽  
Amanda L Tauber ◽  
Stephan M Levonis ◽  
Stephanie S Schweiker
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Parp Inhibitors ◽  
In Vitro Assays ◽  
Inhibiting Activity ◽  
Design Synthesis ◽  
In Silico Studies ◽  
Amine Compounds ◽  
Potential Inhibitors

Poly(ADP-ribose) polymerase (PARP) members PARP1 and PARP14 belong to an 18-member superfamily of post-translational modifying enzymes. A library of 9 novel non-NAD analog amine compounds was designed, synthesized and evaluated for inhibitory activity against PARP1 and PARP14. Both in silico studies and in vitro assays identified compound 2 as a potential PARP1 inhibitor, inhibiting activity by 93 ± 2% (PARP14 inhibition: 0 ± 6%), and 7 as a potential PARP14 inhibitor, inhibiting activity by 91 ± 2% (PARP1 inhibition: 18 ± 4%), at 10-μm concentration. Key in silico interactions with TYR907 in PARP1 and TYR1620 and TYR1646 in PARP14 have been identified. Compound 2 and compound 7 have been identified as potential leads for the development of selective PARP inhibitors.

Synthesis, in vitro $$\alpha $$ α -glucosidase inhibitory activity, and in silico study of (E)-thiosemicarbazones and (E)-2-(2-(arylmethylene)hydrazinyl)-4-arylthiazole derivatives

2018 ◽  
Vol 22 (4) ◽  
pp. 841-861 ◽  
Author(s):  
Muhammad Ali ◽  
Khalid Mohammed Khan ◽  
Uzma Salar ◽  
Mohammed Ashraf ◽  
Muhammad Taha ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
In Silico Study

Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory activity, and in silico study of S-naproxen derivatives

2019 ◽  
Vol 83 ◽  
pp. 29-46 ◽  
Author(s):  
Ghulam Mohiuddin ◽  
Khalid Mohammed Khan ◽  
Uzma Salar ◽  
Kanwal ◽  
Muhammad Arif Lodhi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
In Silico Study ◽  
Drug Synthesis ◽  
Urease Inhibitory

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.

Computational and In-Vitro Validation of Natural Molecules as Potential Acetylcholinesterase Inhibitors and Neuroprotective Agents

2019 ◽  
Vol 16 (2) ◽  
pp. 116-127 ◽  
Author(s):  
Ashwani Kumar ◽  
Vineet Mehta ◽  
Utkarsh Raj ◽  
Pritish Kumar Varadwaj ◽  
Malairaman Udayabanu ◽  
...  
Keyword(s):  
In Silico ◽  
Hippocampal Neurons ◽  
Symptomatic Relief ◽  
In Vitro Assays ◽  
Disease Modifying Drugs ◽  
In Silico Docking ◽  
Ache Inhibitors ◽  
Significant Difference ◽  
Disease Modifying

Background: Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer’s disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is used to identify new and safer ‘disease-modifying drugs’. Methods: Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism. Further, the potential of the predicted molecules to inhibit acetylcholinesterase (AChE) activity and their ability to protect neurons from degeneration was determined through in-vitro assays. Results: Based on in-silico AChE interaction studies, we predicted quercetin, caffeine, ascorbic acid and gallic acid to be potential AChE inhibitors. We confirmed the AChE inhibitory potential of these molecules through in-vitro AChE inhibition assay and compared results with donepezil and begacestat. Herbal molecules significantly inhibited enzyme activity and inhibition for quercetin and caffeine did not show any significant difference from donepezil. Further, the tested molecules did not show any neurotoxicity against primary (E18) hippocampal neurons. We observed that quercetin and caffeine significantly improved neuronal survival and efficiently protected hippocampal neurons from HgCl2 induced neurodegeneration, which other molecules, including donepezil and begacestat, failed to do. Conclusion: Quercetin and caffeine have the potential as “disease-modifying drugs” and may find application in the management of neurological disorders such as AD.

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