In Silico Pharmacology最新文献

{"title":"Identification of immucillin analogue natural compounds to inhibit <i>Helicobacter pylori</i> MTAN through high throughput virtual screening and molecular dynamics simulation.","authors":"Divya S Raj,&nbsp;Chidhambara Priya Dharshini Kottaisamy,&nbsp;Waheetha Hopper,&nbsp;Umamaheswari Sankaran","doi":"10.1007/s40203-021-00081-2","DOIUrl":"https://doi.org/10.1007/s40203-021-00081-2","url":null,"abstract":"<p><strong>Abstract: </strong>One in every two humans is having <i>Helicobacter pylori</i> (<i>H. pylori</i>) in stomach causing gastric ulcer. Emergence of several drugs in eliminating <i>H. pylori</i> has paved way for emergence of multidrug resistance in them. This resistance is thriving and thereby necessitating the need of a potent drug. Identifying a potential target for medication is crucial. Bacterial 5'-methylthioadenosine/<i>S</i>-enosyl homocysteine nucleosidase (MTAN) is a multifunctional enzyme that controls seven essential metabolic pathways. It functions as a catalyst in the hydrolysis of the <i>N</i>-ribosidic bond of adenosine-based metabolites: <i>S</i>-adenosylhomocysteine (SAH), 5'-methylthioadenosine (MTA), 5'-deoxyadenosine (5'-DOA), and 6-amino-6-deoxyfutalosine. <i>H. pylori</i> unlike other bacteria and humans utilises an alternative pathway for menaquinone synthesis. It utilises Futosiline pathway for menaquinone synthesis which are obligatory component in electron transport pathway. Therefore, the enzymes functioning in this pathway represent them-self as a point of attack for new medications. We targeted MTAN protein of <i>H. pylori</i> to find out a potent natural hit to inhibit its growth<i>.</i> A comparative analysis was made with potent <i>H. pylori</i> MTAN (<i>Hp</i>MTAN) known inhibitor, 5'-butylthio-DADMe-Immucillin-A (BuT-DADMe-ImmA) and ZINC natural subset database. Optimized ligands from the ZINC natural database were virtually screened using ligand based pharmacophore hypothesis to obtain the most efficient and potent inhibitors for <i>Hp</i>MTAN. The screened leads were evaluated for their therapeutic likeness. Furthermore, the ligands that passed the test were subjected for MM-GBSA with MTAN to reveal the essential features that contributes selectivity. The results showed that Van der Waals contributions play a central role in determining the selectivity of MTAN. Molecular dynamics (MD) studies were carried out for 100 ns to assess the stability of ligands in the active site. MD analysis showed that binding of ZINC00490333 with MTAN is stable compared to reference inhibitor molecule BuT-DADMe-ImmA. Among the natural inhibitors screened after various docking procedures ZINC00490333 has highest binding score for <i>Hp</i>MTAN (- 13.987). The ZINC inhibitor was successful in reproducing the BuT-DADMe-ImmA interactions with <i>Hp</i>MTAN. Hence we suggest that ZINC00490333 compound may represent as a good lead in designing novel potent inhibitors of <i>Hp</i>MTAN. This in silico approach indicates the potential of this molecule for advancing a further step in gastric ulcer treatment.</p><p><strong>Graphic abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00081-2.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00081-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25543421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccinomics approach for scheming potential epitope-based peptide vaccine by targeting l-protein of Marburg virus.","authors":"Tahmina Pervin,&nbsp;Arafat Rahman Oany","doi":"10.1007/s40203-021-00080-3","DOIUrl":"https://doi.org/10.1007/s40203-021-00080-3","url":null,"abstract":"<p><p>Marburg virus is one of the world's most threatening diseases, causing extreme hemorrhagic fever, with a death rate of up to 90%. The Food and Drug Administration (FDA) currently not authorized any treatments or vaccinations for the hindrance and post-exposure of the Marburg virus. In the present study, the vaccinomics methodology was adopted to design a potential novel peptide vaccine against the Marburg virus, targeting RNA-directed RNA polymerase (l). A total of 48 l-proteins from diverse variants of the Marburg virus were collected from the NCBI GenBank server and used to classify the best antigenic protein leading to predict equally T and B-cell epitopes. Initially, the top 26 epitopes were evaluated for the attraction with major histocompatibility complex (MHC) class I and II alleles. Finally, four prospective central epitopes NLSDLTFLI, FRYEFTRHF, YRLRNSTAL, and YRVRNVQTL were carefully chosen. Among these, FRYEFTRHF and YRVRNVQTL peptides showed 100% conservancy. Though YRLRNSTAL showed 95.74% conservancy, it demonstrated the highest combined score as T cell epitope (2.5461) and population coverage of 94.42% among the whole world population. The epitope was found non-allergenic, and docking interactions with human leukocyte antigens (HLAs) also verified. Finally, in vivo analysis of the recommended peptides might contribute to the advancement of an efficient and exclusively prevalent vaccine that would be an active route to impede the virus spreading.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00080-3.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2021-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00080-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25477097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atezolizumab and granzyme B as immunotoxin against PD-L1 antigen; an insilico study.","authors":"Fateme Sefid,&nbsp;Zahra Payandeh,&nbsp;Ghasem Azamirad,&nbsp;Behzad Baradaran,&nbsp;Mohsen Nabi Afjadi,&nbsp;Maryam Islami,&nbsp;Maryam Darvish,&nbsp;Seyed Mehdi Kalantar,&nbsp;Houman Kahroba,&nbsp;Mahnam Alaei Ardakani","doi":"10.1007/s40203-021-00076-z","DOIUrl":"https://doi.org/10.1007/s40203-021-00076-z","url":null,"abstract":"<p><p>CD274 gene encodes programmed death-ligand 1 (PD-L1) protein, also known as B7 homolog 1 (B7-H1), which is a crucial hallmark for highly proliferation cells including cancer cells. PD-1 and PD-L1 interaction is assumed as a negative regulator for immune response which can inhibit the T cell growth and cytokine secretion and supports tumor cells evasion from immune system. therefore, PD-L1 could be assumed as a candidate target for immune-therapy. The predicted structure of PD-L1 indicates (Gly4Ser) 3 linker-based chains links. In that line, different simulation softwares applied to explore the structure of granzyme B (GrB), a serine protease in cytotoxic lymphocytes granules as an apoptosis mediator, was attached to its specific antibody structure (atezolizumab) via an adaptor sequence. Evaluation of accuracy, energy minimization and characterization of biological properties of the final processed structure were performed and our computational outcomes indicated that the employed method for structure prediction has been successfully managed to design the immunotoxin structure. It is necessary to mention that, the precise and accurate design of the immune-therapeutic agents against cancer cells can be confirmed by employment of in-silico approaches. Consequently, based on this approach we could introduce a capable immunotoxin which specifically targeting PD-L1 in an accurate orientation and initiates cancer cell destruction by its toxin domain.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00076-z.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00076-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25445443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico analysis of STX2a-PE15-P4A8 chimeric protein as a novel immunotoxin for cancer therapy.","authors":"Maryam Keshtvarz,&nbsp;Jafar Salimian,&nbsp;Jafar Amani,&nbsp;Masoumeh Douraghi,&nbsp;Ehsan Rezaie","doi":"10.1007/s40203-021-00079-w","DOIUrl":"https://doi.org/10.1007/s40203-021-00079-w","url":null,"abstract":"<p><p>Today, the targeted therapies like the use of immunotoxins are increased which targeted specific antigens or receptors on the surface of tumor cells. Fibroblast growth factor-inducible 14 (Fn14) is a cytokine receptor which involves several intercellular signaling pathways and can be highly expressed in the surface of cancer cells. Since the cleavage of enzymatic domain of <i>Pseudomonas exotoxin A</i> (PE) occurs in one step by furin protease, we fused enzymatic subunit of Shiga-like toxin type 2a (Stx2a) with domain II and a portion of Ib of PE to increase the toxicity of Stx. Then, we genetically fused the Fv fragment of an anti-Fn14 monoclonal antibody (P4A8) to STX2a-PE15 and evaluated the STX2a-PE15-P4A8 chimeric protein as a new immunotoxin candidate. In silico analysis showed that the STX2a-PE15-P4A8 is a stable chimeric protein with high affinity to the Fn14 receptor. Despite, the STX2a-PE15-P4A8 can be bind to the B cell receptor, but it has been weakly presented by major histocompatibility complex molecules II (MHC-II). So, it may have a little immunogenicity. On the basis of our in-silico studies we predict that STX2a-PE15-P4A8 can be a good candidate for cancer immunotherapy.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00079-w.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00079-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25421421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing binding intensity and energetic features of histone deacetylase inhibitor pracinostat towards class I HDAC isozymes through futuristic drug designing strategy.","authors":"Shabir Ahmad Ganai","doi":"10.1007/s40203-021-00077-y","DOIUrl":"https://doi.org/10.1007/s40203-021-00077-y","url":null,"abstract":"<p><p>Pracinostat, an emerging hydroxamate histone deacetylase (HDAC) inhibitor has shown better efficacy than approved inhibitor suberoylanilide hydroxamic acid (SAHA). Apart from haematological malignancies, this inhibitor has shown promising results in preclinical models of solid tumours. Being pan-inhibitor pracinostat targets various classical HDACs and has demonstrated antiproliferative properties in a series of cancer cell lines. Currently, no energetic and structural studies are available about the pracinostat against four HDAC isozymes of Class I. Taking this into account, the current study involved flexible molecular docking for gaining insights regarding pracinostat-HDAC isozyme interactions, molecular mechanics generalized born surface area (MM-GBSA) for estimating binding affinity of this inhibitor towards these isozymes and energetically optimized pharmacophores (e-Pharmacophores) technique for delineating the critical e-pharmacophoric features of pracinostat in its least energy state in the binding pocket of these HDACs. The outcome from this study will help in further optimization of pracinostat towards better therapeutic and the e-Pharmacophores generated will serve as queries in e-Pharamcophores guided virtual screening.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2021-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00077-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25402491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational insight into the protective mechanism of <i>Allium iranicum</i> Wendelbo. Alliaceae in a mouse model of Staphylococcosis: focus on dietary phytocannabinoid <i>trans</i>-caryophyllene.","authors":"Layth Jasim Mohammed, Khosrow Chehri, Isaac Karimi, Nasser Karimi","doi":"10.1007/s40203-021-00078-x","DOIUrl":"10.1007/s40203-021-00078-x","url":null,"abstract":"<p><p>This study was aimed to investigate the prophylactic effects of hydro-alcoholic extract derived from bulbs of <i>Allium iranicum</i> Wendelbo. (Alliaceae; AI) on mouse model of Staphylococcosis, and to decipher which phytochemicals of AI may involve in its anti-staphylococcal property. Male mice were allocated into four groups, i.e. normal control (NC) and three other groups received AI at 0.192, 0.384 and 0.768 mg/ml in drinking water for 9 days. Thereafter, mice were intravenously injected 10⁶ colony forming unites (CFUs/ml) of <i>Staphylococcus aureus</i> suspension at 10th day and tissue homogenates were colony counted for <i>S. aureus</i> 9 days post-inoculation. Molecular docking among cardinal proteins involved in Staphylococcosis and phytochemicals of AI has been performed using PyRx software and the best ligand submitted to compute molecular and biological attributes. Induction of murine Staphylococcosis and inclusion of AI did not adversely alter bodyweights of mice while colony counts in selected tissues of mice infected with <i>S. aureus</i> were different among groups (P_ANOVA = 0.016). Generally, the colony counts tended to decrease in AI 0.192 (P = 0.099) and AI 0.768 (P = 0.818) groups as compared to NC, however AI 0.384 (P = 0.005) group showed lesser colony counts than NC. In addition, colony counts decreased in AI 0.384 as compared to AI 0.768 (P = 0.009). The colony counts in kidneys of AI 0.0384 group were lesser than those of NC (P = 0.051) and AI 0.768 (P = 0.048). Among target proteins, <i>trans</i>-caryophyllene (<i>TCP</i>) showed reliable binding affinities (kcal/mol) to three hydrolase enzymes [beta toxin (sphingomyelin phosphodiesterase - 8.1), sortase B (protease - 8.1), and FtsZ (GTPase - 8.7) of <i>S. aureus</i>]. The ADMET properties of <i>TCP</i> showed that it followed the Lipinski's rule of five with one violation with respect to its miLogP 5.17. In addition, Molinspiration bioactivity score indicated ion channel modulatory and enzyme inhibitory effect for <i>TCP</i>. Computational findings of admetSAR software revealed that <i>TCP</i> leads to carcinogenicity, <i>Tetrahymena pyriformis</i>, fish, rat, and honey bee toxicities, weak inhibition of human ether-a-go-go-related gene, and cytochromes inhibitory promiscuity. The <i>TCP</i> showed promising in human intestinal absorption, blood-brain barrier permeability, Caco-2 penetration, and solubility. The results of Toxtree software showed that <i>TCP</i> is not an endogenous molecule of the body and contains no functional groups associated with enhanced toxicity and considered as class I toxic compound close to terpenes. In conclusion, we found the hydro-alcoholic extract derived from of bulbs AI has a significant protective effect against Staphylococcosis in mouse model. In silico findings demonstrated that <i>TCP</i> has acceptable ADMET score to be considered as a bioactive compound for designing phytobiotics.</p><p><strong>Supplem","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2021-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867674/pdf/40203_2021_Article_78.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25383298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in silico approach to study the interaction of BHA with selected steroid hormone receptors and investigating it's agonistic and antagonistic properties.","authors":"Subin Balachandran,&nbsp;R N Binitha","doi":"10.1007/s40203-020-00070-x","DOIUrl":"https://doi.org/10.1007/s40203-020-00070-x","url":null,"abstract":"<p><p>Antioxidant food additives were routinely used for increasing the keeping quality of packaged food items. Butylated Hydroxyanisole (BHA) is one of the most widely used synthetic phenolic antioxidants of such kind. Although quantity of antioxidants in packaged eatables and admissible daily intake (ADI) per person per day are limited by laws, the urbanisation and changes in lifestyle has cross these limits. Although studies on BHA has been carried out, there exists a great deal of uncertainty about the exact molecular mechanism of interaction of BHA with various receptors in the body. Since earlier reports suggested BHA plausibly interferes with reproductive system development, we opted docking of critical receptors of endogenous hormones controlling growth and development of reproductive system with BHA. Nuclear receptors of estrogen (ER), androgen (AR) and progesterone (PR) were selected for this purpose. This manuscript describes the comparison of binding pattern of BHA towards AR, ER and PR along with their agonists and antagonist. Lamarckian Genetic Algorithm of AutoDock 4.0 was used for analysing the mode of binding of ligands with the receptors. It is evident form the docking studies that, BHA exhibited similar binding pattern` with antagonists of AR and agonists of ER. But the interaction of BHA with PR was not compatible with either agonists or antagonists. The docking patterns produced could reliably demonstrate the interactions of BHA with selected receptors and also predict its possible agonistic and antagonistic action.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2021-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-020-00070-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25316060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization and epitope-based vaccine predictions for <i>ompA</i> gene associated with biofilm formation in multidrug-resistant strains of <i>A.baumannii</i>.","authors":"Deepthi Sogasu,&nbsp;A S Smiline Girija,&nbsp;Shoba Gunasekaran,&nbsp;J Vijayashree Priyadharsini","doi":"10.1007/s40203-020-00074-7","DOIUrl":"https://doi.org/10.1007/s40203-020-00074-7","url":null,"abstract":"<p><p>The present study was conducted to molecularly characterize the biofilm associated <i>ompA</i> gene from the drug resistant strains of <i>A. baumannii</i> and its immuno-dominant vaccine epitope predictions through immuno-informatic approach. <i>ompA</i> was amplified by PCR from the genomic DNA and was sequenced. Using the ORF, ompA protein sequence was retrieved and was subjected for IEDB T cell and B cell epitope analysis for the selection of the epitope peptides. Selected peptides were evaluated using appropriate servers and tools to assess the propensity for its antigenicity, solubility, physico-chemical property, toxigenicity and class-I immunogenicity. MHC class I and II restriction of HLA alleles was also performed. 48% (n = 24) of the strains possessed <i>ompA</i> gene. Protein structure was successfully retrieved with the selection of two epitopes viz., E1- FDGVNRGTRGTSEEGTLGNA and E2-KLSEYPNATARIEGHTDNTGPRKL. Final docking with TLR-2, showed E2 as the best epitope candidate predicted with the highest number of hydrogen bonds.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-020-00074-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25316059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BACE1 and cholinesterase inhibitory activities of compounds from <i>Cajanus cajan</i> and <i>Citrus reticulata</i>: an in silico study.","authors":"Kayode Ezekiel Adewole,&nbsp;Ahmed Adebayo Ishola","doi":"10.1007/s40203-020-00067-6","DOIUrl":"https://doi.org/10.1007/s40203-020-00067-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the major neurodegenerative diseases whose underlying risk factors are yet to be fully understood. However, reduced cellular level of cholinesterase, as well as formation and deposition of amyloid plaques (Aβ) are thought to play critical roles in the pathogenesis of AD. Therefore, increases in cholinergic transmitter levels via cholinesterase (ChE) inhibitors as well as inhibition of amyloid plaques formation and aggregation via beta secretase-1 (BACE1) inhibitors have been proposed as treatment for this disease. This study was aimed at investigating the BACE1 and ChE inhibitory properties of compounds from <i>Cajanus cajan</i> and <i>Citrus reticulata</i> based on their traditional connection with the management of neurodegenerative diseases, coupled with their protective effects on chemical-induced cognitive impairment. Using in silico methods, one hundred and nineteen compounds from <i>C. cajan</i> and <i>C. reticulata</i> were docked with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1 using Vina. Molecular interactions of the top-ranked compounds for the 3 protein targets were viewed with Discovery Studio, followed by characterization of their ADME properties using the Swiss online ADME web tool. Among the one hundred and ninety nine compounds screened, 3 compounds, genistin (<b>76</b>), naphthalen-2-yl-acetic acid, 6-hydroxy-6-methyl-cyclodecyl ester (<b>94</b>) and vitexin (<b>119</b>) have remarkable binding affinity for the three protein targets and passed the oral drugability test, while only naphthalen-2-yl-acetic acid, 6-hydroxy-6-methyl-cyclodecyl ester (<b>94</b>) exhibited BBB permeation property. Genistin and vitexin from <i>C. cajan</i> and naphthalen-2-yl-acetic acid, 6-hydroxy-6-methyl-cyclodecyl ester from <i>C. reticulata</i> possibly contributed, at least in part, to the neurotherapeutic potentials of these plants.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2021-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-020-00067-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25316058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro cholinesterase inhibitory action of <i>Cannabis sativa</i> L. Cannabaceae and in silico study of its selected phytocompounds.","authors":"Isaac Karimi, Namdar Yousofvand, Baydaa Abed Hussein","doi":"10.1007/s40203-021-00075-0","DOIUrl":"10.1007/s40203-021-00075-0","url":null,"abstract":"<p><p><i>Cannabis sativa</i> L. Cannabaceae, used for psychoactive rituals in Mesopotamia. Here, we investigated in vitro inhibitory activity of methyl alcohol extract derived from leaves and resin of cannabis against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, the binding affinity (BA; kcal/mol) of selected phytochemicals of cannabis to AChE and BChE has been predicted in silico. Phytochemicals of cannabis had acceptable BA towards AChE ranging from  - 6.4 (beta-pinene) to  - 11.4 (campesterol) and BChE ranging from  - 5.5 (alpha-pinene) to  - 9.8 (cannabioxepane). All cannabinoids, flavonoids (apigenin), terpenes, and phytosterols of cannabis were double inhibitors due they utilized hydrogen bonds and hydrophobically interacted with both catalytic triad and peripheral anionic site (PAS) of AChE and BChE. Campesterol is phytosterol docked with AChE and BChE via hydrogen bond and it will be a lead-like molecule for further drug design. Delta-9-Tetrahydrocannabinolic acid has been docked with AChE and BChE and it can be a candidate molecule for further drug design. To sum up, this study not only approved cholinesterase inhibitory effects of cannabis but also suggested an array of phytocompounds as hit small molecules for discovery or design of ecofriendly botanical antiinsectants or phytonootropic drugs.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00075-0.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2021-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820056/pdf/40203_2021_Article_75.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25315622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}