scholarly journals Cannabis sativa L. chemical compositions as potential plasmodium falciparum dihydrofolate reductase-thymidinesynthase enzyme inhibitors: An in silico study for drug development

2021 ◽  
Vol 19 (1) ◽  
pp. 1244-1250
Author(s):  
Pham Minh Quan ◽  
Le Thi Thuy Huong ◽  
Tran Quoc Toan ◽  
Nguyen Phi Hung ◽  
Pham Hai Nam ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Development ◽  
Dihydrofolate Reductase ◽  
In Silico ◽  
Cannabis Sativa ◽  
Research Effort ◽  
Chemical Compositions ◽  
Autodock Vina ◽  
Lipinski’S Rule ◽  
Docking Energy

Abstract This study contributes to anti-malarial research effort by conducting in silico assessment of 125 compounds originated from Cannabis sativa L. against plasmodium falciparum dihydrofolate reductase-thymidinesynthase (pfDHFR-TS) enzyme for potential inhibition activity. Drug-like and pharmacokinetic criteria were used to assess the drug-like properties of the studied compounds. AutoDock4.2.6 and AutoDock Vina software were used to calculate the possible binding pose of the studied compounds to pfDHFR-TS enzyme. The docking procedure was validated using two known inhibitors cycloguanil and WR99210. 65 out of 125 compounds violated no more than 2 of Lipinski’s rule of five and were sorted out as favorable for drug development. Amongst these 65 compounds, pharmacokinetic properties and toxicity evaluation identified 60 compounds that meet the criteria of drug-like properties and were subjected to further docking studies. Docking outcomes identified 10 compounds including compounds 4, 9, 19, 22, 23, 25, 30, 42, 43, and 59 as potential candidates for inhibiting the function of pfDHFR-TS at the active site through hydrogen bonds with Ile14, Asp54, and Ile 164 residues. Compound 9 is considered as the top “hit” with docking energy far more exceeding those of the standard compounds. High correlation coefficient between the docking energy of AutoDock4.2.6 and AutoDock Vina was recorded with the value of R 2 = 0.74.

scholarly journals Analysis Docking Of Plasmodium Falciparum Enoyl Acyl Carrier Protein Reductase (Pfenr) With Organic Compunds From Virtual Screening Of Herbal Database

2020 ◽  
Vol 3 (1) ◽  
pp. 127
Author(s):  
Nya Daniaty Malau ◽  
St Fatimah Azzahra
Keyword(s):  
Plasmodium Falciparum ◽  
Virtual Screening ◽  
In Silico ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Chemotherapeutic Agents ◽  
Effective Vaccine ◽  
Carrier Protein ◽  
Autodock Vina ◽  
In Silico Screening

Malaria is one of problematic infectious diseases worldwide. The absence of an effective vaccine and the spread of drug resistant strains of Plasmodium clearly indicate the necessity for the deveploment of new chemotherapeutic agents. Recent method being developed is searching a new drug of antimalarial using in silico screening, or also known as virtual screening. One of enzyme target that important for growth of the malaria parasite is Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR). Inhibition of this enzyme cause the fatty acid biosynthesis type II will be terminated. In this research, in silico screening was performed using AUTODOCK VINA software to find inhibitor candidates of PfENR by using ligands from the database of Medicinal Plants in Indonesia. On the AUTODOCK VINA software moleculer docking experiments were performed between ligands and macromolecule target PfENR. This target that has been optimized with residue removal and charges addition. Ligand is expected to be the PfENR inhibitors.

scholarly journals Naturally occurring phytochemical as inhibitors from Catharanthus roseus: An In-silico approaches for drug development against COVID-19

2020 ◽  
Author(s):  
Rishee K. Kalaria ◽  
Hiren K. Patel
Keyword(s):  
Drug Development ◽  
Catharanthus Roseus ◽  
In Silico ◽  
The Novel ◽  
Key Factors ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Phytochemical Compounds ◽  
Current Outbreak ◽  
Indian Medicine

Abstract The current outbreak of the novel 2019 Coronavirus disease (COVID-19) is caused by SARS-CoV-2, has developed a threat to the world's human population. There are no effective therapies or vaccines yet, urging the serious efforts to tackle this pandemic situation.SARS-CoV-2 spike protein, papain like protease protein (PLPRO), main protease (3CLpro) and RNA dependent DNA polymerase are key factors in the virus infectious process and have been identified as potential targets for therapeutic formulation. Most people in India depend on conventional Indian medicine (phytochemical compounds) to treat diseases due to lower cost, easier accessibility and no adverse effects. A lot of studies have recently shown that phytochemicals contain an effective anti-viral activity. This study aims to investigate phytochemicals metabolites from the IMPPAT database (Indian Medicinal Plants Database) in order to identify potential COVID-19 inhibitors using in silico approaches. Certain phytochemical compounds with structure analogs like hydroxychloroquine and chloroquine from the IMPPAT database were taken for interaction with SARS-CoV-2 proteins. The Apparicine, 12-Chlorotabersonine, AC1NSULH and Vindolininol identified from Catharanthus roseus were further checked the ADMET property as well as ‘Lipinski’s rule and resulted in a strong binding affinity of (-7.6,-7.5) and (-7.6 -7.5) kcal/mol respectively for spikes and papain like protease protein of SARS-CoV-2. Our results indicate that these specific compounds can be used as effective inhibitors and help to pace up the drug development against SARS-CoV-2. Further investigation and testing of these inhibitors against SARS‐CoV‐2 are however required to check their clinical trial candidacy.

Discovery of traditional Chinese medicine derived compounds as wild type and mutant Plasmodium falciparum dihydrofolate reductase inhibitors: Induced fit docking and ADME studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Opeyemi Iwaloye ◽  
Olusola Olalekan Elekofehinti ◽  
Babatomiwa Kikiowo ◽  
Toyin Mary Fadipe ◽  
Moses Orimoloye Akinjiyan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Dihydrofolate Reductase ◽  
Active Sites ◽  
Wild Type ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Lipinski’S Rule ◽  
Drug Candidates

Background: In a bid to come up with effective compounds as inhibitors in antimalarial treatment, we built a library containing about 2,000 traditional Chinese medicine(TCM)-derived compounds retrieved from TCM Data-base@Taiwan. The active sites of both the wild type and mutant Plasmodium falciparum dihydrofolate reductase (pfDHFR) were explored using computational tools. pfDHFR, one of the prime drug targets in the prevention of malaria infection induced by the female anopheles mosquito has continued to coffer resistance to drugs (antifolates) due to mutation in some of the key amino acid residues crucial for its inhibition. Results: We utilized virtual throughput screening and glide XP docking to screen the compounds, and 8 compounds were found to have promising docking score with both the wild type and mutant pfDHFR. They were further subjected to induced fit docking (IFD) to affirm their inhibitory potency. The ADME properties and biological activity spectrum of the com-pounds were also considered. Inspection of the inhibition profile of the compounds demonstrated that a number of the com-pounds form intermolecular interaction with ASP54, ILE14, LEU164, SER108/ASN108, ARG122 and ASP58. Majority of the compounds are considered to be drug candidates due to their antiprotozoal activities and accordance with Lipinski’s rule of five (ROF). Conclusion: The outcome of the present study should further be investigated to attest the efficacy of these compounds as better drug candidates than the antifolates.

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.

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