Molecular docking analysis of mTOR protein kinase with chromatographically characterized compounds from Clerodendrum inerme L. leaves extract

The mTOR protein is known to be linked with cancer. Therefore, it is of interest to document the molecular docking analysis of mTOR protein kinase with chromatographically characterized compounds from Clerodendrum inerme L. leaves extract. The GC-MS analysis suggested that, totally 25 bioactive compounds were present in the extract of Clerodendrum inerme. Molecular docking analysis show that the bioactive compounds such as Triethoxysilanol, Piperazine dihydrochloridehydrate, 2,4(1H,3H)-Pyrimidinedione, 5-methyl and 4'',7-Dihydroxyflavanone showed good glide score and glide energy within the acceptable and permissible limits of ADME properties for further consideration in drug discovery.     

Molecular docking and in vitro analysis of phytoextracts from B. serrata for antibacterial activities

The bioactives of Boswellia serrata have a role in ulcer healing therapies. Eleven bioactive compounds were obtained by GC-MS among which Cholan-24-oic acid, 3,12-bis (acetyl oxy) has a high molecular weight of 490.6719 with a retention time of 26.729. Twenty wound samples were collected aseptically from the labs and hospitals in and around the Namakkal districts of Tamilnadu, India. The antibacterial potential of E.coli showed a maximum inhibition of 27 mm against Tetracycline at 30µg. The ethanolic extract of the B. serrata shows a susceptibility of 19mm towards E. coli at 60µg concentration in MIC. Molecular docking results show the binding energy of Cholan-24-oic acid, 3,12-bis(acetyloxy) -8.6 (kcal/mol) followed by Pyrene, hexadecahydro- -6.7 (kcal/mol), and 5(1H)- Azulenone, 2,4,6,7,8,8a-hexahydro-3,8-dimethyl-4-(1-methylethylidene)-, (8S-cis)- 6.4 (kcal/mol) for further consideration.     

Molecular docking analysis of the BRCA1 protein with compounds from Justica adhatoda L

BRCA1 is a human tumour suppression gene. Therefore, it is of interest to document the Molecular docking analysis data of the BRCA1 protein with compounds from Justica adhatoda L (adhatoda). We report that Amrinone, Hexadecanoic acid, Pyrazinamide & Vasicinone have acceptable binding features with the BRCA1 protein for further consideration.     

Molecular docking study investigating the possible mode of binding of C.I. Acid Red 73 with DNA

C.I. Acid Red 73 is a reactive azo dye with a variable potential carcinogenicity. The mechanism mediating interactions that occur between the dye and DNA have not been completely understood thus far. In this study, molecular docking techniques were applied to describe the most probable mode of DNA binding as well as the sequence selectivity of the C.I. Acid Red 73 dye. These docking experiments revealed that the dye is capable of interacting with the minor groove of the DNA on the basis of its curved shape, which fits well with the topology of double-stranded DNA. In addition, the dye can bind selectively to the minor groove of the DNA by applying CGT sequence selectivity. Further, the minor groove can be recognized although DNA targets present intercalation gaps. However, intercalative binding can also occur when the DNA target possesses an appropriate intercalation gap. Compared with the other eight DNA sequences that were studied, the DNA dodecamer d(CGCGATATCGCG)₂ (PDB ID: 1DNE) presents a very favorable target for the binding of C.I. Acid Red 73 to the minor groove, with the lowest binding free energy −9.19 kcal/mol. Results reported from this study are expected to provide useful information for research involving further simulations of molecular dynamics and toxicology investigations of the dye.     

Bacterial Peptide deformylase inhibition of cyano substituted biaryl analogs: Synthesis,in vitro biological evaluation,molecular docking study and in silico ADME prediction

Herein, we report the synthesis and screening of cyano substituted biaryl analogs 5(a–m) as Peptide deformylase (PDF) enzyme inhibitors. The compounds 5a (IC₅₀ value = 13.16 μM), 5d (IC₅₀ value = 15.66 μM) and 5j (IC₅₀ value = 19.16 μM) had shown good PDF inhibition activity. The compounds 5a (MIC range = 11.00–15.83 μg/mL), 5b (MIC range = 23.75–28.50 μg/mL) and 5j (MIC range = 7.66–16.91 μg/mL) had also shown potent antibacterial activity when compared with ciprofloxacin (MIC range = 25–50 μg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF, the synthesized compounds 5(a–m) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates.     

Molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein

The MUC1 oncoprotein is known to be linked with different types of cancer. Therefore, it is of interest to document the molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein. We report the structure based molecular binding features compounds such as amrinone, ethambutol, pyrazinamide and vasicoline the MUC1 oncoprotein for further consideration in drug discovery.     

Molecular docking analysis of bioactive compounds from Mollugo cerviana (L.) SER with DHFR for antifungal activity

Fungal infections have been increasing in recent years due to growing number of high-risk patients particularly immuno compromised hosts. Candida is the third- or fourth-most-common isolate in nosocomial bloodstream infections. The increase of fungal resistance to classical drugs, the treatment costs, and the fact that most available antifungal drugs have only fungistatic activity, justify the search for new strategies. Identification of therapeutic compounds from plants has been the centre of attraction ever since they were discovered. It is of interest to document the molecular docking analysis of bioactive compounds present in Mollugo cerviana (L.) SER with the DHFR protein target for antifungal activity. We show the optimal binding features of several compounds from the extract with in vivo and in vitro activities. Results of this showed that all compounds showed good antimicrobial activity and a very good antifungal activity against the target DHFR protein. So, these compounds may act as potential drug molecules after the experimental validation.     

Molecular docking elucidates the plausible mechanisms underlying the anticancer properties of acetyldigitoxigenin from Adenium obesum

Adenium obesum (Forssk.) Roem. & Schult. is a promising medicinal plant belonging to the Apocynaceae family. It is a rich source of various phytochemicals such as cardiac glycosides, flavonoids, terpeniods, pregnanes etc. which have different pharmacological properties such as anticancer, antibacterial, acaricidal etc. While previous reports showed the anticancer activity of the aerial parts of the plant extract of A. obesum, the mechanisms of action of its chemical constituents are not known. The present study is aimed at elucidation of plausible mechanisms of anticancer activity of the plant by evaluating the binding interaction of its nine major selected compounds with macromolecular receptors implicated in the initiation and progression of cancer using various in silico approaches. Molecular docking results showed that the compound Δ¹⁶-3-Acetyldigitoxigenin (16-anhydro-3-acetylgitoxigenin) scored the best binding energy scores with the majority of the target proteins. The molecular binding of the compound was stabilized through hydrogen bonds as well as hydrophobic interactions, and also possesses favorable drug-like properties without significant toxicities.     

Molecular mechanism of Ferula asafoetida for the treatment of asthma: Network pharmacology and molecular docking approach

Asthma is a significant health-care burden that has great impact on the quality of life of patients and their families. The limited amount of previously reported data and complicated pathophysiology of asthma make it a difficult to treat and significant economic burden on public healthcare systems. Ferula asafoetida is an herbaceous, monoecious, perennial plant of the Umbelliferae family. In Asia, F. asafoetida is used to treat a range of diseases and disorders, including asthma. Several in vitro studies demonstrated the therapeutic efficacy of F. asafoetida against asthma. Nevertheless, the precise molecular mechanism is yet to be discovered. In the framework of current study, network pharmacology approach was used to identify the bioactive compounds of F. asafoetida in order to better understand its molecular mechanism for the treatment of asthma. In present work, we explored a compound-target-pathway network and discovered that assafoetidin, cynaroside, farnesiferol-B, farnesiferol-C, galbanic-acid, and luteolin significantly influenced the development of asthma by targeting MAPK3, AKT1 and TNF genes. Later, docking analysis revealed that active constituents of F. asafoetida bind stably with three target proteins and function as asthma repressor by regulating the expression of MAPK3, AKT1 and TNF genes. Thus, integration of network pharmacology with molecular docking revealed that F. asafoetida prevent asthma by modulating asthma-related signaling pathways. This study lays the basis for establishing the efficacy of multi-component, multi-target compound formulae, as well as investigating new therapeutic targets for asthma.     

Molecular docking and simulation analysis of the FimH protein with secondary metabolites from the Garcinia species

It is of interest to document the molecular docking and simulation analysis of the FimH protein with 10 secondary metabolites from Garcinia species in the context of drug discovery for Urinary tract infections (UTIs). We report the optimal binding features of flavonoids with the FimH protein for further consideration in drug discovery.     

Molecular modeling of cornulin (CRNN) for docking with phytocompounds from Justicia adhatoda L.

Cornulin (CRNN) is linked with tumour progression. Therefore, it is of interest to document data on the molecular modeling of cornulin (CRNN) for docking with phytocompounds (Pyrazinamide, Anisotine, Vasicinone, Vasicoline) from Justicia adhatoda L. Thus, we document the optimal binding features of these compounds with the cornulin model for further consideration.     

Investigation of the interaction between salvianolic acid C and xanthine oxidase: Insights from experimental studies merging with molecular docking methods

Xanthine oxidase (XO) has emerged as an important target for gout. In our previous study, salvianolic acid C (SAC) was found to show potent XO inhibitory activity, whereas the interaction mechanism was still not clear. Herein, an integrated approach consisting of enzyme kinetics, multi-spectroscopic methods and molecular docking was employed to investigate the interaction between SAC and XO. Consequently, SAC exhibited a rapid and mixed-type inhibition of XO with IC₅₀ of 5.84 ± 0.18 μM. The fluorescence data confirmed that SAC presented a strong fluorescence quenching effect through a static quenching procedure. The values of enthalpy change, entropy change and Gibbs free energy change indicated that their binding was spontaneous and driven mainly by hydrophobic interactions. Analysis of synchronous fluorescence, circular dichroism and fourier transform infrared spectra demonstrated that SAC induced conformational changes of the enzyme. Besides, further molecular docking revealed that SAC occupied the catalytic center resulting in the inhibition of XO activity. This study provides a comprehensive understanding on the interaction mechanism of SAC on XO.     

兴安杜鹃叶中挥发性成分的GC-MS分析

采用水蒸气蒸馏法对兴安杜鹃叶中的挥发性成分进行提取,并运用气相色谱—质谱联用技术(GC-MS)对其挥发性成分进行了系统的分离和鉴定。从兴安杜鹃叶中共鉴定出54种挥发性成分,占总馏出成分的97.84%。兴安杜鹃叶主要挥发性成分为桉叶醇(eduesmol),相对含量10.95%;β-愈创木烯(β-guaiene),相对含量10.21%;长叶醛(longifolenaldehyde),相对含量7.88%;1,5,9,9-四甲基-1,4,7-环十一碳三烯(1,5,9,9-tetramethyl-1,4,7-cy-cloundecatriene),相对含量7.80%;杜鹃酮(germacrone),相对含量5.91%;(-)-葎草烯环氧化物Ⅱ((-)-HumuleneepoxideⅡ),相对含量5.52%;2-庚基-1,3-二氧戊环(2-heptyl-1,3-dioxolane),相对含量4.99%;石竹烯(caryo-phyllene),相对含量3.70%;(+)-γ-古芸烯((+)-γ-gurjunene),相对含量3.44%。     

Molecular docking analysis of estrogen receptor binding phytocomponents identified from the ethyl acetate extract of Salicornia herbacea (L)

It is of interest to evaluate the secondary metabolites using high performance thin layer chromatography (HPTLC) finger printing and Gas chromatography-Mass spectroscopy (GC-MS) in S. herbaceaextract. The powdered plant material extracted using different solvents were used for the qualitative analysis of alkaloids, flavonoids, terpenoids and saponins followed by HPTLC finger printing and GC-MS analysis. The components identified in the GC-MS were docked with estrogen receptor (ER) to identify the binding specificity of isolated compounds. The ethyl acetate extract of S. herbaceashowed the presence of high number of secondary metabolites when compared to other solvent system. The qualitative analysis of the plant material also showed the presence of carbohydrates, protein, amino acid, phenol, flavonoids, terpenoids, glycosides, saponins and steroids. The HPTLC finger printing analysis revealed the existence of alkaloid, flavonoid, terpenoid and saponin compounds and GC-MS. GC-MS was performed to identify the phytocomponents constituents in the extract. 8 phytocompounds were identified to analyse binding with ER. The binding affinity score (-6.8 kcal/mol) and interacting ER residues (28) the phyto compound di-n-octyl phthalate showed best docking score with ER α than the standard drugs lasofoxifene, and 4-hydroxytamoxifen. The binding affinity and number of interacting ER residues was -6.9 kcal/mol; 10 and -6.2; 11, respectively. The results identified the presence of ER antagonist in S. herbaceaand warrants further investigation to explore for treating ER regulated diseases.     

Molecular designing,virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR

The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is ?8.5?kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >?9.20?kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients.     

石山巴豆与毛果巴豆叶中挥发油成分分析

采用水蒸气蒸馏法提取石山巴豆和毛果巴豆叶中的挥发油,利用GC-MS联用仪对其化学成分进行分析和鉴定,以归一化法计算各个化学成分的相对含量。结果表明:从石山巴豆叶鉴定出39种化合物,占总量的95.96%,主要成分是α-松油醇(17.57%)、桉树醇(11.13%)、乙酸松油酯(9.07%)、倍半水芹烯(8.52%)等;从毛果巴豆叶鉴定出55种化合物,占总量的97.8%,以反式-橙花叔醇(9.48%)、α-松油醇(7.51%)、桉树醇(6.43%)、乙酸松油酯(6.72%)为主要成分。两种植物叶中的挥发油成分均以萜醇、倍半萜烯为主,并且其中多种成分具有生物活性,因此研究结果可为石山巴豆和毛果巴豆的开发利用提供科学依据。     

Inhibitory effect on soybean lipoxygenase and docking studies of some secondary metabolites,isolated from Origanum vulgare L. ssp. hirtum

In this study, five secondary metabolites (caffeic acid, rosmarinic acid, lithospermic acid B, 12-hydroxyjasmonic acid 12-O-β-glucoside and p-menth-3-ene-1,2-diol 1-O-β-glucopyranoside) isolated from the polar extracts of the plant Origanum vulgare L. ssp. hirtum, were tested in vitro for their ability to inhibit soybean lipoxygenase. Among the examined compounds, lithospermic acid B demonstrated the best inhibitory activity on soybean lipoxygenase with IC₅₀ = 0.1 mM. Docking studies have been undertaken as an attempt for better understanding the interactions of these compounds within the active site of soybean lipoxygenase. The predicted binding energy values correlated well with the observed biological data.     

Phenolic compounds and antioxidants from Eucalyptus camaldulensis as affected by some extraction conditions,a preparative optimization for GC-MS analysis

Abstract

Four organic solvents along with water were applied for the conventional extraction of Eucalyptus camaldulensis (Myrtaceae), phenolic contents and antioxidant activities were investigated through variable protocols and correlation coefficients were considered, the phenolic composition was also characterized by Gas chromatography-mass spectrometry (GC-MS). Using solvents with dissimilar polarities affected the phenolic yields extracted from E. camaldulensis and their related antioxidant activities varied significantly among the four investigated plant organs. The leaf extract of acetone 70% contained the highest amount of phenolic compounds (46.56?mg/g dry weight); while the bud-water boiled extract maintained the maximum value of tannins (45.68?mg/g dry weight). Correlation coefficients indicated that phenolic compounds were mostly accountable for the phosphomolybednum antioxidant potentials (0.520), followed by tannins (0.460). Also, both the reducing power activities and hydrogen peroxide scavenging of E. camaldulensis extracts positively correlated with tannins, but at different significance degrees. However, the GC-MS analysis revealed that most of the detected phenolic constituents were more abundant in the plant seed. So, the existence of some other compounds such as organic acids, along with phenolics, may have increased the antioxidant potentials of leaf and bud. Undeniably, the optimization of extraction conditions could stimulate the antioxidant capabilities of the plant extracts of E. camaldulensis.