Computer-Aided Prediction and Identification of Phytochemicals as Potential Drug Candidates against MERS-CoV

The Middle East respiratory syndrome coronavirus (MERS-CoV) is the major leading cause of respiratory infections listed as blueprint of diseases by the World Health Organization. It needs immediate research in the developing countries including Saudi Arabia, South Korea, and China. Still no vaccine has been developed against MERS-CoV; therefore, an effective strategy is required to overcome the devastating outcomes of MERS. Computer-aided drug design is the effective method to find out potency of natural phytochemicals as inhibitors of MERS-CoV. In the current study, the molecular docking approach was employed to target receptor binding of CoV. A total of 150 phytochemicals were docked as ligands in this study and found that some of the phytochemicals successfully inhibited the catalytic triad of MERS-CoV. The docking results brought novel scaffolds which showed strong ligand interactions with Arg178, Arg339, His311, His230, Lys146, and Arg139 residues of the viral domains. From the top ten ligands found in this study (i.e., rosavin, betaxanthin, quercetin, citromitin, pluviatilol, digitogenin, ichangin, methyl deacetylnomilinate, kobusinol A, and cyclocalamin) based on best S -score values, two phytochemicals (i.e., pluviatilol and kobusinol A) exhibited all drug-likeness properties following the pharmacokinetic parameters which are important for bioavailability of drug-like compounds, and hence, they can serve as potential drug candidates to stop the viral load. The study revealed that these phytochemicals would serve as strong potential inhibitors and a starting point for the development of vaccines and proteases against MERS-CoV. Further, in vivo studies are needed to confirm the efficacy of these potential drug candidates.

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Cationic Diclofenac Lipid Nanoemulsion for Improved Oral Bioavailability: Preparation, Characterization and In Vivo Evaluation

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.2.10 ◽

2015 ◽

Vol 8 (2) ◽

pp. 2874-2880

Author(s):

Kishan Veerabrahma ◽

Swapna Madishetty ◽

Muzammil Afzal Syed ◽

Prabhakar Kandadi

Keyword(s):

Oral Bioavailability ◽

Physical Stability ◽

Cationic Lipid ◽

Entrapment Efficiency ◽

In Vivo Studies ◽

Pharmacokinetic Parameters ◽

In Vivo Evaluation ◽

Drug Content ◽

Lipid Nanoemulsion

Cationic nanoemulsions were reported to have increased bioavailability. The aim of present study was to prepare a cationic lipid nanoemulsion of diclofenac acid (LNEs) for improved oral bioavailability to treat arthritic conditions. The LNEs of diclofenac acid were prepared by using soya bean oil, egg lecithin, cholesterol and stearylamine. Stearylamine was used as positive charge inducer. The LNEs were processed by homogenization and ultrasonication. The formulation composition was selected based on earlier reports. The LNEs were characterized for size and zeta potential. The physical stability of LNEs was studied using autoclaving, centrifugal, desorption (dilution effect) stresses and on storage. The total drug content and entrapment efficiency were determined using HPLC. During in vivo studies in Wistar rats, the pharmacokinetic parameters of LNEs were compared with a prepared diclofenac suspension in sodium CMC mucilage. The selected formulations, F1, F2 and F3, were relatively stable during centrifugal stress, dilution stress and on storage. The drug content was found to be 2.38 ± 1.70 mg/ml for F1, 2.30 ± 0.82 mg/ml for F2, and 2.45 ± 0.66 mg/ml for F3. The entrapment efficiencies were 97.83 ± 0.53%, 97.87 ± 1.22% and 98.25 ± 0.21% for F1, F2 and F3 respectively. The cumulative percentage drug release from F1, F2 and F3 showed more release in pH 6.8 phosphate buffer than in pH 1.2 HCl. During oral bioavailability studies, the LNEs showed higher serum concentrations than a suspension. The relative bioavailability of the LNE formulations F1, F2 and F3 were found to be 2.35, 2.94 and 6.28 times that of F4 suspension and were statistically significant. Of all, the cationic lipid nanoemulsion (F3) was superior in improving bioavailability, when compared with plain emulsion (F1) and cholesterol containing LNE (F2). The study helps in designing the cationic oral nanoemulsions to improve the oral bioavailability of diclofenac.

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Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

Current Medicinal Chemistry ◽

10.2174/0929867325666180117142142 ◽

2018 ◽

Vol 25 (21) ◽

pp. 2503-2519 ◽

Cited By ~ 4

Author(s):

Anne Kokel ◽

Marianna Torok

Keyword(s):

Side Effects ◽

Antimicrobial Peptides ◽

Potential Drug ◽

Green Technologies ◽

Specific Antibodies ◽

Structural Modifications ◽

Drug Candidates ◽

Induce Resistance ◽

Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

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Novel Phytochemical Constituents and their Potential to Manage Diabetes

Current Pharmaceutical Design ◽

10.2174/1381612826666201222154159 ◽

2020 ◽

Vol 26 ◽

Author(s):

Shaik Ibrahim Khalivulla ◽

Arifullah Mohammed ◽

Kokkanti Mallikarjuna

Keyword(s):

Natural Products ◽

Large Population ◽

World Health ◽

In Vivo Studies ◽

Antidiabetic Activity ◽

Therapeutic Drug ◽

Pharmacological Activities ◽

Chemical Structures

Background: Diabetes is a chronic disease affecting a large population worldwide and stands as one of the major global health challenges to be tackled. According to World Health Organization, about 400 million are having diabetes worldwide and it is the seventh leading cause of deaths in 2016. Plant based natural products had been in use from ancient time as ethnomedicine for the treatment of several diseases including diabetes. As a result of that, there are several reports on plant based natural products displaying antidiabetic activity. In the current review, such antidiabetic potential compounds reported from all plant sources along with their chemical structures are collected, presented and discussed. This kind of reports are essential to pool the available information to one source followed by statistical analysis and screening to check the efficacy of all known compounds in a comparative sense. This kind of analysis can give rise to few numbers of potential compounds from hundreds, whom can further be screened through in vitro and in vivo studies, and human trails leading to the drug development. Methods: Phytochemicals along with their potential antidiabetic property were classified according to their basic chemical skeleton. The chemical structures of all the compounds with antidiabetic activities were elucidated in the present review. In addition to this, the distribution and their other remarkable pharmacological activities of each species is also included. Results: The scrutiny of literature led to identification of 44 plants with antidiabetic compounds (70) and other pharmacological activities. For the sake of information, the distribution of each species in the world is given. Many plant derivatives may exert antidiabetic properties by improving or mimicking the insulin production or action. Different classes of compounds including sulfur compounds (1-4), alkaloids (5-11), phenolic compounds (12-17), tannins (18-23), phenylpropanoids (24-27), xanthanoids (28-31), amino acid (32), stilbenoid (33), benzofuran (34), coumarin (35), flavonoids (36-49) and terpenoids (50-70) were found to be active potential compounds for antidiabetic activity. Of the 70 listed compounds, majorly 17 compounds are from triterpenoids, 13 flavonoids and 7 are from alkaloids. Among all the 44 plant species, maximum number (7) of compounds are reported from Lagerstroemia speciosa followed by Momordica charantia (6) and S. oblonga with 5 compounds. Conclusion: This is the first paper to summarize the established chemical structures of phytochemicals that have been successfully screened for antidiabetic potential and their mechanisms of inhibition. The reported compounds could be considered as potential lead molecules for the treatment of type-2 diabetes. Further, molecular and clinical trials are required to select and establish the therapeutic drug candidates.

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Predicting Absorption-Distribution Properties of Neuroprotective Phosphine-Borane Compounds Using In Silico Modeling and Machine Learning

Molecules ◽

10.3390/molecules26092505 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2505

Author(s):

Raheem Remtulla ◽

Sanjoy Kumar Das ◽

Leonard A. Levin

Keyword(s):

Machine Learning ◽

Neural Networks ◽

In Silico ◽

Disulfide Bonds ◽

Oral Absorption ◽

In Vivo Studies ◽

Drug Candidates ◽

In Silico Methods

Phosphine-borane complexes are novel chemical entities with preclinical efficacy in neuronal and ophthalmic disease models. In vitro and in vivo studies showed that the metabolites of these compounds are capable of cleaving disulfide bonds implicated in the downstream effects of axonal injury. A difficulty in using standard in silico methods for studying these drugs is that most computational tools are not designed for borane-containing compounds. Using in silico and machine learning methodologies, the absorption-distribution properties of these unique compounds were assessed. Features examined with in silico methods included cellular permeability, octanol-water partition coefficient, blood-brain barrier permeability, oral absorption and serum protein binding. The resultant neural networks demonstrated an appropriate level of accuracy and were comparable to existing in silico methodologies. Specifically, they were able to reliably predict pharmacokinetic features of known boron-containing compounds. These methods predicted that phosphine-borane compounds and their metabolites meet the necessary pharmacokinetic features for orally active drug candidates. This study showed that the combination of standard in silico predictive and machine learning models with neural networks is effective in predicting pharmacokinetic features of novel boron-containing compounds as neuroprotective drugs.

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In Silico Screening of Potential Drug with Antileishmanial Activty and Validation of their Activity by in Vitro and in Vivo Studies

Journal of Chemistry and Chemical Engineering ◽

10.17265/1934-7375/2015.06.002 ◽

2015 ◽

Vol 9 (6) ◽

Cited By ~ 1

Author(s):

Carol V. Mesa ◽

Gustavo A. Blandón ◽

Diana L. Muñoz ◽

Carlos E. Muskus ◽

Andrés F. Flórez ◽

...

Keyword(s):

In Silico ◽

In Vivo Studies ◽

Potential Drug ◽

In Silico Screening

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Gold (III) Derivatives in Colon Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms23020724 ◽

2022 ◽

Vol 23 (2) ◽

pp. 724

Author(s):

Agata Gurba ◽

Przemysław Taciak ◽

Mariusz Sacharczuk ◽

Izabela Młynarczuk-Biały ◽

Magdalena Bujalska-Zadrożny ◽

...

Keyword(s):

Protein Structures ◽

Thioredoxin Reductase ◽

Structural Similarity ◽

In Vivo Studies ◽

Antitumor Effects ◽

Solubility In Water ◽

Physiological Conditions ◽

Drug Candidates ◽

New Methods

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

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Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021

Frontiers in Pharmacology ◽

10.3389/fphar.2021.659577 ◽

2021 ◽

Vol 12 ◽

Author(s):

Safaet Alam ◽

Taslima Binte Kamal ◽

Md. Moklesur Rahman Sarker ◽

Jin-Rong Zhou ◽

S. M. Abdur Rahman ◽

...

Keyword(s):

Clinical Trials ◽

Case Series ◽

Basic Knowledge ◽

World Health ◽

Current Status ◽

Drug Candidates ◽

Health Organization ◽

Meta Analyses

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

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Medicinal Utility of Some Schiff Bases and their Complexes with First Transition Series Metals: A Review

Oriental Journal Of Chemistry ◽

10.13005/ojc/370506 ◽

2021 ◽

Vol 37 (5) ◽

pp. 1051-1061

Author(s):

Tahmeena Khan ◽

Saima Zehra ◽

Almas Alvi ◽

Umama Fatima ◽

Alfred J. Lawrence

Keyword(s):

Transition Metal ◽

Metal Complexes ◽

Transition Metal Complexes ◽

Present Review ◽

Potential Drug ◽

Drug Candidates ◽

Transition Series ◽

Low Toxicity ◽

Activity Enhancement

Schiff based ligands and their complexes have emerged as potential drug candidates. Owing to their excellent chelating tendency, they easily coordinate with transition metals which have vacant orbitals. Transition metal complexes have several advantages because of their better acceptability and low toxicity in biological systems. These metals also serve as micronutrients and as co-factors of various metallo-enzymes which justifies the need of their designing and synthesis. Many modifications have been suggested in the ligand moiety for the purpose of activity enhancement and some of them have been described in the present review. These modifications have enhanced better potency against a number of diseases and resulting in low toxicity and better solubility in vivo. The transition metal complexes with Schiff based complexes have exhibited an array of activities including anticancer, antioxidant and antimicrobial. Their analytical applications have also been reported. The present review summarizes some of the recent advances in the field of synthesis and designing of new Schiff based complexes particularly with first transition series metals and their medicinal applications.

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