New 3d Multifunctional Metal Chelates of Sulfonamide: Spectral, Vibrational, Molecular Modeling, DFT, Medicinal and In Silico Studies

2022 ◽  
pp. 132305
Author(s):  
Abrar Ul Hassan ◽  
Sajjad Hussain Sumrra ◽  
Muhammad Imran ◽  
Zahid Hussain Chohan
Keyword(s):  
Molecular Modeling ◽  
In Silico ◽  
Metal Chelates ◽  
In Silico Studies

Synthesis, pharmacological assessment, molecular modeling and in silico studies of fused tricyclic coumarin derivatives as a new family of multifunctional anti-Alzheimer agents

2016 ◽  
Vol 107 ◽  
pp. 219-232 ◽  
Author(s):  
Jeelan Basha Shaik ◽  
Bhagath Kumar Palaka ◽  
Mohan Penumala ◽  
Kasi Viswanath Kotapati ◽  
Subba Rao Devineni ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
In Silico ◽  
Coumarin Derivatives ◽  
New Family ◽  
In Silico Studies

Enhanced solubility of Albendazole in Cyclodextrin Inclusion Complex: A Molecular Modeling Approach and Physicochemical Evaluation

2021 ◽  
Vol 18 ◽  
Author(s):  
Camila Gomes de Melo ◽  
Lucas Amadeu Costa Gonzaga ◽  
Marcelo Montenegro Rabello ◽  
Victor de Albuquerque Wanderley Sales ◽  
Aline Silva Ferreira ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Inclusion Complexes ◽  
In Silico ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Scanning Calorimetry ◽  
Kneading Method ◽  
In Silico Studies ◽  
Enhanced Solubility

Background: Albendazole (ABZ) is the drug of choice for the treatment of a variety of human and veterinary parasites. However, it has low aqueous solubility and low bioavailability. Cyclodextrins (CD) are pharmaceutical excipients with the ability to modulate the solubilization property of hydrophobic molecules. Objective: To analyze (Autodock Vina software and CycloMolder platform) the formation of inclusion complexes between ABZ, β-cyclodextrin (β-CD) and its derivatives, Methyl-β-cyclodextrin (M-β-CD) and Hydroxypropyl-β-cyclodextrin (HP-β-CD), through in vitro and in silico studies. Methods: The most stable inclusion complexes were produced by the kneading method and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), determination of the ABZ content, and in vitro dissolution profile. Results: Molecular modeling revealed that inclusion complexes between HP-β-CD:ABZ (in the proportion 1:1 and 2:1) presented the lowest formation energy and the highest number of intermolecular interactions, showing that the use of more cyclodextrins does not provide any gain in the stability of the complex. Through the characterization tests, the complexes experimentally obtained by kneading method demonstrated a highly suggestive method, including ABZ in HP-β-CD in both molar proportions; The results of this study showed suppression of bands in the infrared spectrum, displacement of the drug's melting temperature in DSC, crystallinity halos instead of the characteristic peaks of ABZ crystals in the XRD and a release of more than 80% of ABZ in less than 5 minutes, beyond dissolution efficiency of up to 92%. Conclusion: In silico studies provided a rational selection of the appropriate cyclodextrin, enabling the elaboration of more targeted complexes, decreasing time and costs to elaborate on new formulations that increase the oral biodisponibility of ABZ.

In Silico Identification of Novel APRIL Peptide Antagonists and Binding Insights by Molecular Modeling and Immunosorbent Assays

2015 ◽  
Vol 22 (5) ◽  
pp. 432-442 ◽  
Author(s):  
Joao Silva ◽  
Flavia Calmon-Hamaty ◽  
Wilson Savino ◽  
Michael Hahne ◽  
Ernesto Caffarena
Keyword(s):  
Molecular Modeling ◽  
In Silico ◽  
Immunosorbent Assays

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

2020 ◽  
Vol 28 (2) ◽  
pp. 213-237 ◽  
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.

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

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.

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.

Promising Anticancer Therapeutics From Mushrooms: Current Findings and Future Perceptions

2020 ◽  
Vol 21 ◽  
Author(s):  
Mrunmaya Kumar Panda ◽  
Manish Paul ◽  
Sameer Kumar Singdevsachan ◽  
Kumananda Tayung ◽  
Swagat Kumar Das ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
In Silico ◽  
Present Review ◽  
Cancer Cell Proliferation ◽  
Research Papers ◽  
Medicinal Mushrooms ◽  
In Silico Studies ◽  
Anticancer Therapeutics ◽  
Ethnomedicinal Uses

Background: Nowadays medicines derived from natural sources have drawn much attention as potential therapeutic agents in the suppression and treatment of cancer because of their low toxicity and fewer side effects. Objective: The present review aims to assess the currently available knowledge on the ethnomedicinal uses and pharmacological activities of bioactive compounds obtained from medicinal mushrooms towards cancer treatment. Methods: Literature search has been conducted for the collection of research papers from universally accepted scientific databases. These research papers and published book chapters were scrutinized to retrieve information on ethnomedicinal uses of mushrooms, different factors involved in cancer cell proliferation, clinical and in silico pharmaceutical studies made for possible treatments of cancer using mushroom derived compounds. Overall 241 articles were retrieved and reviewed from the year of 1970 to 2020, out of which 98 relevant articles were finally considered for preparation of this review. Results: This review presents an update on the natural bioactive substances derived from medicinal mushrooms and their role in inhibiting the factors responsible for cancer cell proliferation. Along with it, the present review also provides information on the ethnomedicinal uses, solvents used for extraction of anticancer metabolites, clinical trials, and in silico studies that were undertaken towards anticancer drug development from medicinal mushrooms. Conclusion: The present review provides an extensive knowledge on various anticancer substances obtained from medicinal mushrooms, their biological actions and in silico drug designing approaches which could form a basis for the development of natural anticancer therapeutics.

In Vitro, In Silico and Ex Vivo Studies of Dihydroartemisinin Derivatives as Antitubercular Agents

2019 ◽  
Vol 19 (8) ◽  
pp. 633-644 ◽  
Author(s):  
Komal Kalani ◽  
Sarfaraz Alam ◽  
Vinita Chaturvedi ◽  
Shyam Singh ◽  
Feroz Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Silico ◽  
Ex Vivo ◽  
Virulent Strain ◽  
Infection Model ◽  
Mouse Bone Marrow ◽  
Significant Activity ◽  
Macrophage Infection ◽  
In Silico Studies

Introduction: As a part of our drug discovery program for anti-tubercular agents, dihydroartemisinin (DHA-1) was screened against Mtb H37Rv, which showed moderate anti-tubercular activity (>25.0 µg/mL). These results prompted us to carry out the chemical transformation of DHA-1 into various derivatives and study their antitubercular potential. Materials and Methods: DHA-1 was semi-synthetically converted into four new acyl derivatives (DHA-1A – DHA-1D) and in-vitro evaluated for their anti-tubercular potential against Mycobacterium tuberculosis H37Rv virulent strain. The derivatives, DHA-1C (12-O-(4-nitro) benzoyl; MIC 12.5 µg/mL) and DHA-1D (12-O-chloro acetyl; MIC 3.12µg/mL) showed significant activity against the pathogen. Results: In silico studies of the most active derivative (DHA-1D) showed interaction with ARG448 inhibiting the mycobacterium enzymes. Additionally, it showed no cytotoxicity towards the Vero C1008 cells and Mouse bone marrow derived macrophages. Conclusion: DHA-1D killed 62% intracellular M. tuberculosis in Mouse bone marrow macrophage infection model. To the best of our knowledge, this is the first-ever report on the antitubercular potential of dihydroartemisinin and its derivatives. Since dihydroartemisinin is widely used as an antimalarial drug; these results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non-toxic natural product.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

Coumarinyl Aryl/Alkyl Sulfonates with Dual Potential: Alkaline Phosphatase and ROS Inhibitory Activities: In-Silico Molecular Modeling and ADME Evaluation

2019 ◽  
Vol 16 (3) ◽  
pp. 256-272
Author(s):  
Uzma Salar ◽  
Khalid Mohammed Khan ◽  
Syeda Abida Ejaz ◽  
Abdul Hameed ◽  
Mariya al-Rashida ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Alkaline Phosphatase ◽  
Molecular Modeling ◽  
In Silico ◽  
Smooth Muscles ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Selective Inhibitors ◽  
Specific Alkaline Phosphatase ◽  
Inhibitory Activities

Background: Alkaline Phosphatase (AP) is a physiologically important metalloenzyme that belongs to a large family of ectonucleotidase enzymes. Over-expression of tissue non-specific alkaline phosphatase has been linked with ectopic calcification including vascular and aortic calcification. In Vascular Smooth Muscles Cells (VSMCs), the high level of Reactive Oxygen Species (ROS) resulted in the up-regulation of TNAP. Accordingly, there is a need to identify highly potent and selective inhibitors of APs for treatment of disorders related to hyper activity of APs. </P><P> Methods: Herein, a series of coumarinyl alkyl/aryl sulfonates (1-40) with known Reactive Oxygen Species (ROS) inhibition activity, was evaluated for alkaline phosphatase inhibition against human Tissue Non-specific Alkaline Phosphatase (hTNAP) and Intestinal Alkaline Phosphatase (hIAP). </P><P> Results: With the exception of only two compounds, all other compounds in the series exhibited excellent AP inhibition. For hIAP and hTNAP inhibition, IC50 values were observed in the range 0.62-23.5 &#181;M, and 0.51-21.5 &#181;M, respectively. Levamisole (IC50 = 20.21 &#177; 1.9 &#181;M) and Lphenylalanine (IC50 = 100.1 &#177; 3.15 &#181;M) were used as standards for hIAP and hTNAP inhibitory activities, respectively. 4-Substituted coumarinyl sulfonate derivative 23 (IC50 = 0.62 &#177; 0.02 &#181;M) was found to be the most potent hIAP inhibitor. Another 4-substituted coumarinyl sulfonate derivative 16 (IC50 = 0.51 &#177; 0.03 &#181;M) was found to be the most active hTNAP inhibitor. Some of the compounds were also found to be highly selective inhibitors of APs. Detailed Structure-Activity Relationship (SAR) and Structure-Selectivity Relationship (SSR) analysis were carried out to identify structural elements necessary for efficient and selective AP inhibition. Molecular modeling and docking studies were carried out to rationalize the most probable binding site interactions of the inhibitors with the AP enzymes. In order to evaluate drug-likeness of compounds, in silico ADMETox evaluation was carried out, most of the compounds were found to have favorable ADME profiles with good predicted oral bioavailability. X-ray crystal structures of compounds 38 and 39 were also determined. </P><P> Conclusion: Compounds from this series may serve as lead candidates for future research in order to design even more potent, and selective inhibitors of APs.

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