Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies

Abstract Endophytes, notably obtaining attention, have been abided by potential origins of bioactive metabolites. In the acquaint study, endophyte was isolated from the leaves of Nephelium lappaceum L. The chosen endosymbiont was identified by 16s rRNA partial genome sequencing and investigated for their antioxidant and antidiabetic activities. A preliminary phytochemical test was comported for the affirmation of phytoconstituents in endophytic crude extract (NLM). Antioxidant activities were conducted by using 2-diphenyl-1-picrylhydrazyl (DPPH) method and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) method to screen the radical scavenging potential. The evaluation of antidiabetic activities was done by using α-amylase and α-glucosidase inhibition assay. Qualitative phytochemical test on NLM affirmed the presence of phenols, carbohydrates, alkaloids, flavonoids, steroids, mucilage and glycosides. In silico parameters were also specified for antidiabetic activities. The antioxidant assay of NLM expressed proficient antioxidant activity of IC50±SEM 1.35±0.03 µg/mL and IC50±SEM 1.47±0.03 µg/mL, for ABTS and DPPH respectively. Antidiabetic assay results evidenced dose dependent percentage inhibition of the enzyme. The results testified estimable inhibition of α-amylase (IC50±SEM 2.549±0.08 µg/mL) and α-glucosidase inhibition (IC50±SEM 2.29±0.03µg/mL) compared to the standard drug (Acarbose). In silico study divulged that the ellagic acid component present in the plant was responsible for antidiabetic activity. Thus, the study shows that NLM has a wellspring of natural source of antioxidants and antidiabetic agents and furtherance of studies on its mechanism is recommended to know detailed facts.

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Antimicrobial and antioxidant activities of hydrocarbon and oxygenated monoterpenes against some foodborne pathogens through in vitro and in silico studies

Pesticide Biochemistry and Physiology ◽

10.1016/j.pestbp.2019.05.008 ◽

2019 ◽

Vol 158 ◽

pp. 185-200 ◽

Cited By ~ 10

Author(s):

Mohamed E.I. Badawy ◽

Gehan I.Kh. Marei ◽

Entsar I. Rabea ◽

Nehad E.M. Taktak

Keyword(s):

Foodborne Pathogens ◽

In Silico ◽

Antioxidant Activities ◽

Oxygenated Monoterpenes ◽

In Silico Studies

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Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents: Design, Synthesis, Biological Evaluation, SAR and in silico Studies

Current Pharmaceutical Design ◽

10.2174/1381612827666211116102031 ◽

2021 ◽

Vol 27 ◽

Author(s):

Bharti Rajesh Kumar Shyamlal ◽

Manas Mathur ◽

Dharmendra K. Yadav ◽

Irina V. Mashevskaya ◽

Mohamed El-Shazly ◽

...

Keyword(s):

Platelet Aggregation ◽

In Silico ◽

Antioxidant Activities ◽

In Silico Analysis ◽

Antiplatelet Agents ◽

Docking Studies ◽

Biological Evaluation ◽

Design Synthesis ◽

In Silico Studies

Background: Several natural/synthetic molecules having structure similar to 1H-isochromen-1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of molecular framework, have been explored for their antioxidant or antiplatelet activities. Introduction: Based on literature, a new prototype i.e., 3-phenyl-1H-isochromen-1-ones based compounds have been rationalized to possess both antioxidant as well as antiplatelet activities. Consequently, no reports are available regarding its inhibition either by cyclooxygenase-1 (COX-1) enzyme or by arachidonic acid (AA)-induced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxidant and antiplatelet agents. Methods: The goal of this work to identify new 3-phenyl-1H-isochromen-1-ones based compounds via synthesis of a series of analogues and performing in vitro antioxidant as well as AA-induced antiplatelet activities and then, identification of potent compounds by SAR and molecular docking studies. Results: Out of all synthesized 3-phenyl-1H-isochromen-1-ones analogues, five compounds showed 7-folds to 16-folds highly potent antioxidant activities than ascorbic acid. Altogether, ten 3-phenyl-1H-isochromen-1-one analogues displayed antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Almost, all the 3-phenyl-1H-isochromen-1-one analogues exhibited potent AA-induced antiplatelet activity; few of them displayed 7-folds more activity as compared to aspirin. Further, in silico analysis validated the wet results. Conclusion: We disclose the first detailed study for the identification of 3-phenyl-1H-isochromen-1-one analogues as highly potent antioxidant as well as antiplatelet agents. The article describes the scaffold designing, synthesis, bioevaluation, structure-activity relationship and in silico studies of pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.

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Isolation, characterization, anticancer and antioxidant activities of 2-methoxy mucic acid from Rhizophora apiculata: An in vitro and in silico studies

10.21203/rs.3.rs-787592/v1 ◽

2021 ◽

Author(s):

A. Parthiban ◽

Sachithanandam V ◽

P. Lalitha ◽

Jayaraman Muthukumaran ◽

Monika Jain ◽

...

Keyword(s):

In Silico ◽

Antioxidant Activities ◽

Antioxidant Property ◽

Dynamics Simulation ◽

Mucic Acid ◽

Rhizophora Apiculata ◽

In Silico Studies ◽

Ft Ir ◽

First Time

Abstract In this present study, the sugar based bioactive molecule, 2-methoxy mucic acid ( 4) was isolated for the first time from the methanolic extract from the leaves of Rhizophora apiculata . The structure of compound was well characterized by different spectroscopic analysis, including FT-IR, 1 H, 13 C NMR spectroscopy and HRMS. Anticancer activity of 2-methoxy mucic acid ( 4 ) was evaluated against HeLa and MDA-MB231 cancer cell lines and they displayed promising activity with the IC 50 values of 22.88283±0.72 µg/ml in HeLa and 2.91925±0.52 µg/ml in case of MDA-MB231, respectively. The antioxidant property of 2-methoxy mucic acid ( 4 ) was found to be (IC 50 ) 21.361±0.41 µg/ml. Apart from in vitro studies, we also performed extensive in silico studies (molecular docking and molecular dynamics simulation) on four key anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-w, Bcl-xL and Bcl-B) towards 2-methoxy mucic acid ( 4) and the results revealed that this molecule showed higher binding affinity towards Bcl-B protein ( ΔG = -5.8 kcal/mol) and the structural stability of Bcl-B protein was significantly improved upon binding of this molecule. The present study affords key insights about the importance of 2-methoxy mucic acid ( 4 ), and thus leads to open the therapeutic route for anticancer drug discovery process.

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In vitro Antioxidant and Anticholinesterase Activities of Ouratea fieldingiana (Gardner) Eng. Leaf Extract and Correlation with Its Phenolics Profile with an in silico Study in Relation to Alzheimer’s Disease

Journal of the Brazilian Chemical Society ◽

10.21577/0103-5053.20210163 ◽

2022 ◽

Author(s):

Lucas Frota ◽

Daniela Alves ◽

Leonardo Freitas ◽

Francisco Lopes ◽

Marcia Marinho ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

In Silico ◽

Antioxidant Activities ◽

Biological Properties ◽

Northeastern Brazil ◽

Acetylcholinesterase Inhibition ◽

In Silico Studies ◽

Phenolic Constituents

Ouratea fieldingiana is a native medicinal plant from Northeastern Brazil and many biological properties are due to the phenolic constituents. The objective of this work was performing the characterization of O. fieldingiana leaf constituents to correlate with antioxidant and anticholinesterase activities by in vitro and in silico studies and thus contribute to find new agents against Alzheimer’s disease. The high-performance liquid chromatography revealed the presence of the flavonoids rutin, isoquercitrin, kaempferol-3-O-rutinoside, quercetin, apigenin and amentoflavone. The antioxidant activities by the (2,2-diphenyl-1-picrylhydrazyl) (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methodologies, showed good results with half maximal inhibitory concentration (IC50) values ranging from 5.63 to 11.47 μg mL-1 and 2.72 to 23.71 μg mL-1, respectively. Acetylcholinesterase inhibition assay pointed out the flavone apigenin with best activity. Computational studies evaluated the interaction of flavonoids with the enzyme acetylcholinesterase co-crystallized with the galantamine, used as standard. All flavonoids exhibited binding energy greater than that of galantamine, but only apigenin showed strong interaction with the active site of the enzyme and other bind probably to different allosteric centers. Then, O. fieldingiana extract and flavonoids with good anti-radical activity and presenting a broad-spectrum action against acetylcholinesterase (AChE) enzyme ought to be tested in clinical studies to discover new neuro-therapeutic candidates.

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Critical Review on the Chemical Aspects of Cannabidiol (CBD) and Harmonization of Computational Bioactivity Data

Current Medicinal Chemistry ◽

10.2174/0929867327666200210144847 ◽

2020 ◽

Vol 28 (2) ◽

pp. 213-237 ◽

Cited By ~ 5

Author(s):

Andrea Mastinu ◽

Giovanni Ribaudo ◽

Alberto Ongaro ◽

Sara Anna Bonini ◽

Maurizio Memo ◽

...

Keyword(s):

In Silico ◽

Cannabis Sativa ◽

Therapeutic Potential ◽

The Novel ◽

In Silico Studies ◽

Computational Data ◽

Synthetic Approaches ◽

Analytical Approaches ◽

Yield Sensitivity ◽

Therapeutic Profile

: Cannabidiol (CBD) is a non-psychotropic phytocannabinoid which represents one of the constituents of the “phytocomplex” of Cannabis sativa. This natural compound is attracting growing interest since when CBD-based remedies and commercial products were marketed. This review aims to exhaustively address the extractive and analytical approaches that have been developed for the isolation and quantification of CBD. Recent updates on cutting-edge technologies were critically examined in terms of yield, sensitivity, flexibility and performances in general, and are reviewed alongside original representative results. As an add-on to currently available contributions in the literature, the evolution of the novel, efficient synthetic approaches for the preparation of CBD, a procedure which is appealing for the pharmaceutical industry, is also discussed. Moreover, with the increasing interest on the therapeutic potential of CBD and the limited understanding of the undergoing biochemical pathways, the reader will be updated about recent in silico studies on the molecular interactions of CBD towards several different targets attempting to fill this gap. Computational data retrieved from the literature have been integrated with novel in silico experiments, critically discussed to provide a comprehensive and updated overview on the undebatable potential of CBD and its therapeutic profile.

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Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

Current Pharmaceutical Design ◽

10.2174/1381612826666201112143230 ◽

2020 ◽

Vol 26 ◽

Author(s):

John Chen ◽

Andrew Martin ◽

Warren H. Finlay

Keyword(s):

Drug Delivery ◽

In Silico ◽

Local Drug Delivery ◽

In Vivo Studies ◽

Intranasal Drug Delivery ◽

Nasal Sprays ◽

In Silico Studies ◽

Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

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

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180220125406 ◽

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.

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