Bond Energy Values Research Articles

Physicochemical, ADMET Properties, and Molecular Docking Studies of N-benzoyl-N’-naphtylthiourea Derivatives for Anti-Breast Cancer Activity

Background: N-benzoyl-N'-naphthylthiourea (BNTU) is a thiourea-derived compound that is predicted to have anti-breast cancer activity. However, their physicochemical properties, ADMET, and receptor-specific targets for their anti-breast cancer activity have not been reported. Objective: This study aimed to predict the physicochemical properties, ADMET, and anti-breast cancer activity of BNTU and its derivatives by in silico approach. Methods: The physicochemical and ADMET properties were predicted using the pkCSM online program and ProTox-II online tool. While the anti-breast cancer activity was predicted using the molecular docking method through the Molegro Virtual Docker (MVD) program on the HER-2 receptor. The parameter observed in the molecular docking method was the bond energy value or rerank score (RS). Compounds with small RS values were predicted to have a great activity. Results: Most BNTU derivatives had lower RS values than BNTU, especially 4TBBNTU, and 4CFBNTU, although their RS values were still higher than lapatinib and TAK-285. As for the reference ligand hydroxyurea, the RS value of BNTU and its derivatives was much lower. The physicochemical and pharmacokinetic properties (ADMET) of lapatinib and TAK-285 were not better than that of BNTU and its derivatives. Conclusion: Five compounds that deserve to be synthesized and tested for anti-breast cancer activity in vitro and in vivo are 4TBBNTU, 3CFBNTU, 4CFBNTU, 4OCBNTU, and the lead compound BNTU.

MOLECULAR DOCKING ANALYSIS AND ADMET PREDICTION Of Caesalpinia sappan COMPOUNDS AS ANTIINFLAMMATORY THROUGH CYCLOOXYGENASE-2 INHIBITION

Selective COX-2 inhibitors have been considered safer treatments than NSAIDs for inflammation from its side effect. Sappanwood was already known for its antiinflammatory activity, but its selectivity towards COX-2 has not been tested. The purpose of this study was to determine the potential activity of compounds in Caesalpinia sappan as anti-inflammatory agents by inhibiting COX-2 and determine their ADMET’s properties through in silico study. Qulified compound from Lipinski’s rule of five evaluation would be continued to the molecular docking using Autodock Tools and ADMET prediction using SwissADME and ADMETLab. Three compounds known to have the best free bond energy (ΔG) values were Caesalpiniaphenol A, Sappankalkon, and Deoxysappanone B with ΔG values respectively (-9.36 ; -9.23 ; -9.02 kcal/mol) and their inhibition constant values of (124.44 ; 172.43 ; 244.75 nM) respectively. Amino acid residues that are known to involve to the formation of hydrogen bonds in ligands are GLN 192 and PHE518. Toxicity results showed that these three compounds were predicted to be neither hepatotoxic nor hERG inhibitors, but 3-deoxysappanone B and sappankalkon was predicted to cause AMES mutagenicity and skin sensitivity. It can be concluded that these third compound has the potential as an inhibitor of the COX-2 enzyme.

IN SILICO STUDY: SECONDARY METABOLITES FROM JAMBOLAN (Syzygium Cumini L.) AS POTENTIAL BREAST CANCER TREATMENTS

Breast cancer ranks second in world cancer incidence rates in 2020, contributing to 2,261,419 new cases, or 11.7% of all new cancer cases globally. The search for cancer drugs that work selectively continues to be encouraged to obtain safe and effective therapy, particularly those derived from medicinal plants. Jambolan is a plant that can thrive in both subtropical and tropical climates, including Indonesia. Jambolan (Syzygium cumini L.) has 89% antioxidant activity and 69% cytotoxic activity against T47D cells. Pharmacophore modelling and molecular docking were used to study the binding of 117 active jambolan drugs to alpha and beta estrogen receptors. Rutin was found to be potentially selective for ER-Beta receptors, with a fit score of 53.13. Molecular docking to ER-Beta revealed that rutin has breast cancer activity with a free bond energy value of -10.5 kcal/mol and better conformation and affinity than native ligands (genistein). It also binds to essential amino acids as an anticancer breast at ARG 346 and GLU 305. Lipinski's rule of five prediction results and in silico ADMET prediction from rutin yielded results that met the candidate drug's parameters. Rutin is a potential therapeutic option for treating breast cancer by targeting the ER-Beta receptor.

Molecular docking and toxicity analysis of ribosome-inactivating protein and natural chemical compounds as promising antiretroviral candidates against HIV-1

Background: HIV (human immunodeficiency virus) uses HIV-1 reverse transcriptase as the receptor to convert RNA into viral DNA. In addition, the CD4 receptor is also used by the virus to enter CD4+ T cells and subsequently replicate. Objective: To screen several proteins in Indonesian plants for the potential to bind to the CD4 receptor. Method: Molecular docking was carried out on Cluspro 2.0 specifically for protein to protein and MOE for protein to ligand. Results: The protein ligands were Cinnamomin III, Agglutinin, PAP, PAP-S, Momordin I, MAP30, Beta-luffin, Luffaculin I, Cucurmosin, DAP, Dianthin-30, Bouganin, Maize, Ricin, Abrin, Balsamin, and the bond energy values (Joules/kg.mol) were -602.8, -973.5, -511.3, -439.1, -532.2, -661.9, -487.0, -472.8, -530.9, -413.6, 444.1, -504.5, -617.2, -855.6, -883.9, -558.6, respectively. The best binding energy with CD4 was selected to identify the compound's molecule. These compounds were abrusin, abrusogenin, eicosadienoic acid, heneicosane, precatorine, and trigonelline, and the bond energy values (Joules/kg.mol) were -19.2158, -16.7057, -15.5155, -13.9632, -15.6119, and -9.2620, respectively. The toxicity test of abrusin was carried out against 18 targets, and two targets showed toxic activities. Conclusion: The content of RIP and natural chemical compounds in Abrus precatorius seeds make them the best candidate for antiretroviral therapy against HIV-1.

Pinostrobin and its derivatives as novel anti-breast cancer agents against human oestrogen receptor alpha: In silico studies of ADMET, docking, and molecular dynamics

Background: Breast cancer is the main cause of cancer death among women. The issue is more complex due to the side effects and resistance of the currently used breast cancer drugs. Pinostrobin, a compound found in Boesenbergia pandurata, has anticancer activity. Modifying the structure of pinostrobin can improve drug bioavailability, reduce toxicity, and work more selectively. Objective: This study aimed to predict the potentials of pinostrobin and its derivatives as anti-breast cancer agents against human oestrogen receptors by an in silico approach. Methods: The pkCSM was utilised to predict the ADMET characteristics. The interaction of ligands with the binding site of the human oestrogen receptor alpha with PDB ID 3ERT was used for molecular docking using MOE, and AMBER was then used for molecular dynamic simulation. Results: Pinostrobin pentanoate had good pharmacokinetic properties and was neither mutagenic nor hepatotoxic. Based on molecular docking, it was more potent compared to pinostrobin, with binding free energy values of -7.849 kcal/mol. Furthermore, in the interaction stability evaluation using 100 ns molecular dynamic simulation by the MM-GBSA calculation method, pinostrobin pentanoate had a stable interaction with a total bond energy value of -9.943 kcal/mol. Conclusion: Pinostrobin pentanoate has the potential as an anti-breast cancer alternative through the human oestrogen receptor alpha.

The Influence of Eugenol in Lubrication Properties of Crude Jatropha Curcas Lin

In machining processes, vegetable oil based lubricant has very promising future to substitute petroleum based lubricant. Due to sustainability issue, lubricants from natural resources is sought after as complement or even substitute for non renewable lubricants. Jatropha curcas Lin oil (JCO) is one of such natural oil. When tested as lubricant, JCO demonstrates good performance and decomposition properties. The research on JCO usually study the performance the oil by characterizing of friction reduced parameters and rarely to analyze deeper in terms of the role of molecular interaction between components of vegetable oil and metal surfaces. To analyses the moleculer interaction, a commercially available software for molecular interaction simulation is employed. In order to simulate the interactions, the procedure of simulation are firstly construct molecular model of JCO components. The model then is employed as basis for the software to calculate interactive forces of each atom or molecule with the neighboring one thru their positions. From the simulation results, it was concluded that value of dipole moment, polarisability, and bond energy of Jatropha oil compound decreased when the concentration of eugenol is increasing. The conclusion is hold true up to 20% of eugenol additon.

Green synthesis of Ag nanoparticles from Verbascum insulare Boiss. and Heldr.: Evaluation of antimicrobial, anticancer, antioxidant properties and photocatalytic degradation of MB

In recent years, due to the environmental friendliness of nanoparticle production, biosynthesis methods using plant extracts and possible physical, chemical, thermal and biological properties of the synthesized nanoparticles are frequently the subject of research. In the present study, hydrothermally assisted synthesis of Ag nanoparticles using twig-leaf extract of Verbascum insulare Boiss. and Heldr., (VIE-AgNPs) a plant endemic to Turkey, was successfully carried out for the first time in this study. The presence of 24 of the 53 phytochemicals investigated in the content of the extract of Verbascum insulare Boiss. and Heldr. (VIE) determined by the LC-MS/MS system was detected. In addition, the amount of phenolic substance involved in reduction was found to be 60.42 ± 9.11 µg Gallic acid equivalent/mg-extract. The synthesized AgNPs were characterized by UV–visible spectra (UV–vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transforms infrared spectroscopy (FTIR), and X-ray diffraction (XRD). In particular, the surface plasmon band observed at 422 nm, the characteristic peaks observed in XRD, and the bond energy values seen in XPS strongly confirmed the formation of AgNPs. XRD and TEM data showed that AgNPs had an average size range of 25–30 nm. FTIR data indicated the presence of some herbal agents on the surface of AgNPs. The properties of the VIE-AgNPs were compared in vitro with chemically produced AgNPs (C-AgNPs). The OSI level of C-AgNPs was 87.78 ± 1.75 AU, while that of VIE- AgNPs was 110.42 ± 7.54 AU. It was observed that the nanoparticle and VIE used in the study had antimicrobial activity. It was determined that its antibacterial activity was stronger than its antifungal activity. When the analyzed inflammatory parameter levels (TNF-α, IL1β, TGF-β, and DEF-β2) were examined, the effect of VIE on inflammation in A549 cells could not be detected. However, it was determined that VIE-AgNPs, one of the nanoparticles used in the study, increased anti-inflammatory levels more than C-AgNPs. When the received data are evaluated together, it can be said that biosynthesized AgNPs suppress proliferation and stimulate apoptosis in cancer cells by increasing oxidative stress and inflammation levels compared to chemical AgNPs, thus showing an anticarcinogenic effect. It was found that VIE-AgNPs could effectively degrade the water pollutant methylene blue (MB) dye. VIE-AgNP mediated 78 % photocatalytic degradation of MB in 180 min. All superior biological properties are thought to be due to the low particle size and the interaction of active components with AgNPs during the biosynthesis process. Because it has been observed that VIE-AgNPs, which have a smaller particle size, have higher biological (cytotoxic, anticarcinogenic, inflammatory, etc.) activities than C-AgNPs. It can be said that AgNPs produced by biosynthesis may have potential use in the production of environmentally friendly, antibacterial/anticarcinogenic materials.

Quantification of hydrogen bond energy based on equations using spectroscopic, structural, QTAIM-based, and NBO-based descriptors which calibrated by the molecular tailoring approach

ContextHydrogen bonds critically influence the structure and properties of both organic molecules and biomolecules, as well as supramolecular assemblies. For this reason, the development and elaboration of methods for quantitative assessment of hydrogen bond energy is an urgent challenge. In this study, using a large series of hydroxycarbonyl aliphatic compounds with the O‒H···O = C intramolecular hydrogen bond, a bank of hydrogen bond descriptors was created, including spectroscopic, structural, QTAIM-based, and NBO-based parameters. It was shown that the O‒H vibration frequency, OH chemical shift as the spectroscopic descriptors, the O···H hydrogen bond length, O···O distance, and O‒H covalent bond length as the structural descriptors, the electron density and its Laplacian, electron potential energy density in the hydrogen bond critical point, the electron density at the ring critical point as the QTAIM-based descriptors change in a correlated manner. The same correlation is found in change of the charge transfer energy through a hydrogen bond, the occupancy of the O‒H bond antibonding orbital, the Wiberg indices of the O···H hydrogen bond, and the O‒H covalent bond, as well as the polarization of the O‒H bond, which are the NBO-based descriptors. It was also recognized that the specified descriptors from the spectroscopic, structural, QTAIM-based, and NBO-based categories are functionally related to the values of intramolecular hydrogen bond energy, quantified via the molecular tailoring approach. This allowed one to obtain a system of equations for quantitative estimation of intramolecular hydrogen bond energy based on the spectroscopic, structural, QTAIM, and NBO descriptors, which makes such quantification more dependable and reliable.MethodsTo obtain the spectroscopic descriptors, the vibrational spectra and shielding constants were calculated using the GIAO method. Structural descriptors were obtained for the equilibrium geometry of molecules, calculated at the MP2(FC)/6–311 + + (2d,2p) level using the Gaussian 09 program. The QTAIM-based descriptors were calculated using the AIMAll program within the framework of the quantum theory “Atoms in Molecules.” The NBO-based descriptors were calculated using the NBO 3.1 program implemented into Gaussian 09. To quantify the energy of intramolecular hydrogen bonds, molecular fragmentation was used within the molecular tailoring approach.

Effective Ion Charges in Ion Exchangers and Electrolyte Solutions

Structures, effective numbers of charges and molecular orbitals of ion pairs and representative fragments of a sulfocation exchanger in various ionic forms were calculated by the non-empirical quantum chemical method of LCAO MO. The effective charges of ions in accordance with the principles of the molecular orbital method were fractional values. For contact ion pairs, where the effective ion charges were experimentally measured by X-ray absorption spectroscopy, we obtained full agreement with the calculated values. The charge numbers of cations and anions differed in both hydrate-separated and ion-exchange systems due to the fact that the oxygen atoms of hydrated water molecules influenced the formation of molecular orbitals. According to the obtained values of the numbers of charges and interionic distances, the energies of the electrostatic interaction of ions were calculated using the integral form of Coulomb's law. Experimental values of the energies of chemical bonds of counterions and fixed ions were obtained using the conductometric contact-difference method when measuring the specific electrical conductivity of MK-40 cation exchange membranes in the range of 20-50oC and according to the Arrhenius equation. The coordination of experimental and calculated chemical bond energies in the ion exchanger was achieved after the addition of hydrogen bond energy to the electrostatic interaction energy. In order to be able to completely nonempirically calculate the energies of chemical bonds in an ion exchanger, we took the value of the hydrogen bond energy as the excitation energy of the first energy level of deformation vibrations of water molecules having a value of 19.4 kJ/mol. A comparison of the contribution of the electrostatic interaction to the total binding energy of alkali metal cations with a fixed ion showed its small role in ion exchange and membrane transport, so that in the first approximation we can say that the transfer of alkali metal cations is determined by the breaking of the hydrogen bond. For cations of a larger charge (calcium), the electrostatic energy already makes a significant contribution, and for trivalent ions, the energies of the Coulomb interaction and hydrogen bonding are close to each other. The soliton mechanism of translation of the energy of deformation vibrations along a chain of water molecules is considered, which allows explaining the decrease in energy when several hydrogen bonds are broken.

Analysis of Molecular Docking and Dynamics Simulation of Mahogany (Swietenia macrophylla King) Compounds Against the PLpro Enzyme SARS-COV-2

Background: Using natural ingredients as antivirals can be considered a treatment for SARS-CoV-2. One of the potential plants, mahogany (Swietenia macrophylla King), is widely used in various countries as an antiviral treatment. Paparin-like protease (PLpro) is an essential cysteine ​​protease that regulates viral replication and interferes with the regulation of immune sensing. Objective: This study aims to predict which compounds in the mahogany plant have good affinity, patterns, and stability interaction against the target protein of SARS-CoV-2. Methods: The drug-likeness parameter using SwissADME was used to screen compounds that will be docked against PLpro using the Autodock program. The parameters observed in molecular docking analysis are the value of bond energy and interaction model to amino acid residues. The compounds in mahogany plants that have the best interactions were then analyzed using molecular dynamics simulation methods to determine the stability of their bonds based on the values of Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF). Results: Twenty-two compounds met the drug-likeness requirements. Molecular docking analysis showed that the compounds predicted to have the best binding affinity and have an interaction pattern similar to natural ligands towards the molecular target of PLpro are 7-deacetoxy-7-oxogedunin and 3β-hydroxy-stigmast-5-en-7-one. The molecular dynamics simulation results revealed that based on the RMSD and RMSF values, the compound 3β-hydroxy-stigmast-5-en-7-one showed higher stability than 7-deacetoxy-7-oxogedunin. Conclusion: 3β-hydroxy-stigmast-5-en-7-one and 7-deacetoxy-7-oxogedunin were predicted to have good interaction with PLPro; however, 3β-hydroxy-stigmast-5-en-7-one showed the higher interaction stability.

IN SILICO STUDY OF EUCALYPTOL FROM EUCALYPTUS GLOBULUS LABILL. AGAINST ANGIOTENSIN-CONVERTING ENZYME AS AN ANTIHYPERTENSIVE IN COVID-19 COMORBID

Objective: This study aimed to determine the best compound from the 62 compounds of Eucalyptus globulus Labill. as an antihypertensive based on its interaction with angiotensin-converting enzyme (ACE) using the in silico study.
 Methods: The study was carried out in silico through molecular docking simulations, analysis of potential compounds using Lipinski’s rule, and ligand-based ADMET prediction on 62 compounds of the E. globulus.
 Results: It was found that eucalyptol (1,8-cineole) had the best interaction with the ACE as indicated by a bond energy value (∆G) of-6.40 kcal/mol with an inhibition constant of 20.82 µM, and interacted with key amino acid residues in captopril, namely HIS513, HIS353, TYR523, and ALA354. Eucalyptol also had good physicochemical properties by fulfilling Lipinski’s rule and had the best ADMET profile compared to other compounds.
 Conclusion: Eucalyptol was the best antihypertensive against ACE based on amino acid residue interaction, physicochemical properties, and ADMET profile.

Calculation of the Electronic Properties Phthalocyanine (H2Pc), Silicon Phthalocyanine (Sipc), Phosphorus Phthalocyanine (PPc) and Energy Gap by the AM1 Method

Many semi-empirical methods are available in Gaussian 16. This patch enables analytical gradients and frequencies in addition to increasing efficiency by replacing the code from MOPAC open source, AM1 and PM3 technologies. In the case of a pure molecule, the values of total energy, bond energy, electronic energy, and nuclear energy (-170.893, -1496.855, -4332.708, 45) Kcal/mol have been successively added. After adding Si and P to the free Phthalocyanine molecule, the values transformed to (-133.30, -4987.486, -1294.027, 11.607) Kcal/mol. For the two resulting molecules (PcSi and PcP), the values became (-136.108, -4858.63, -9354.14, 79.930) Kcal/mol. Notably, the first number indicated an increase. Specifically, for total energy numbers, there was a decrease from -170.893 to -133.3 Kcal/mol when adding Si, and a decrease to -136.108 Kcal/mol when adding P. Overall, the energy value increased with both additions, but the bonding energy notably decreased with Si (-1496.855 to -4987.486 Kcal/mol) and P (-4858.63 Kcal/mol). Electronic energy increased from -4332.708 to -1294.027 Kcal/mol when Si was added. Nuclear energy decreased from 45.036 to 11.607 Kcal/mol when Si was added (increasing to 79.930 Kcal/mol with P). The Heat of Formation (H.o.F.) in Kcal/mol equaled 1565.04 when P was added, 1193.384 when Si was added, and 1531.528 when P was added again. The substantial impact of silicon on Phthalocyanine was evident. Furthermore, the dipole moment of the Phthalocyanine molecule, initially at D 3.687, decreased to D 2.093 and D 4.137 when Si was added first and P the second time, showcasing the significant impact of P due to its high atomic number. Determining the HOMO and LUMO and computing the values of Wavenumber, Wavelength, and Symmetry for the three molecules provided a clear illustration. The computation of electrical potential, electronic orbitals, and energy gap revealed an electronic density of 0.346 eV in the case of the free molecule H2Pc, 5.006 eV in the molecule PPc, and 5.660 eV in the case of SiPc. This offers a comprehensive understanding of the impact of adding P and Si to H2Pc.

Docking study and molecular dynamic approach to predicting the activity of 4-(4-methoxy)benzoyloxy-3-methoxycinnamic acid against COX-1 enzyme

Background: Ferulic acid is a phenolic acid compound that has anti-inflammatory and anti-thrombosis activity. However, ferulic acid has the disadvantage of poor absorption. Structural modifications can be made to increase the biological activity of the compound. In this research, the structure of ferulic acid was modified into 4-(4-methoxy)benzoyloxy-3-methoxycinnamic acid. Objective: The purpose of this research is to predict the activity of 4-(4-methoxy)benzoyloxy-3-methoxycinnamic acid. Method: It was carried out using the Pass Online Prediction, Autodock 1.5.7, Discovery Studio and Maestro Schrödinger 2020-1 software. Result: The activity prediction results showed that 4-(4-methoxy)benzoyloxy-3-methoxycinnamic acid had anti-inflammatory and anti-thrombotic activity. The molecular docking results showed that 4-(4-methoxy)benzoyloxy-3-methoxycinnamic acid had lower free bond energy values than ferulic acid, hence, predicted to have greater activity. Molecular dynamics also reveal better stability interactions of the 4-(4-methoxy)benzoyloxy-3-methoxycinnamic acid with COX-1 protein than the ferulic acid. Conclusion: The compund, 4-(4-methoxy)benzoyloxy-3-methoxycinnamic acid is feasible to be synthesised.

THE POTENTIAL OF INDONESIAN MARINE NATURAL PRODUCT WITH DUAL TARGETING ACTIVITY THROUGH SARS-COV-2 3CLPRO AND PLPRO: AN IN SILICO STUDIES

Objective: This research was conducted to find potential candidate compounds from one hundred thirty-seven Indonesian marine natural products capable of preventing SARS-CoV-2 with a computational approach. Methods: The physicochemical properties and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile of compounds were predicted using ADMETLab. The candidate compounds were filtered using AutodockVina. Molecular docking was carried out using AutoDockTools on the SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) and Papain-like protease (PLpro) that is essential for the SARS-CoV-2 life cycle. Also, AMBER22 was used to perform molecular dynamics simulations in this study. Results: Based on molecular docking results, Pre-Neo-Kaluamine has good activity against 3CLpro with a bond energy value of-10.35 kcal/mol. Cortistatin F showed excellent binding activity on PLpro, with energy value results of-10.62 kcal/mol. Acanthomanzamine C has dual targeting activity and interacts well with protein 3CLpro and PLpro with binding energy values ranging from 10 kcal/mol to 14 kcal/mol. Conclusion: The molecular docking results were corroborated by molecular dynamics simulation results and showed good stability of the candidate ligands, and we found that there were three potential compounds as protease inhibitors of SARS-CoV-2 including Pre-Neo-Kaluamine for 3CLpro, Cortistatin F for PLpro, and Acanthomanzamine C which had dual targeting activity against both proteases.

Designing and property prediction of a novel three-component CL-20/HMX/TNAD energetic cocrystal explosive by MD method.

Cocrystallization technology can effectively regulate crystal structure, alter packing mode, and improve physicochemical performances of energetic materials at molecule level. CL-20/HMX cocrystal explosive has high energy density than HMX, but it also exhibits high mechanical sensitivity. To decrease the sensitivity and improve the properties of CL-20/HMX energetic cocrystal, the three-component energetic cocrystal CL-20/HMX/TNAD was designed. The properties of CL-20, CL-20/HMX, and CL-20/HMX/TNAD cocrystal models were predicted. The results show that CL-20/HMX/TNAD cocrystal models have better mechanical properties than CL-20/HMX cocrystal model, implying that the mechanical properties can be effectively improved. The binding energy of CL-20/HMX/TNAD cocrystal models is higher than CL-20/HMX cocrystal model, indicating that the three-component energetic cocrystal is more stable, and the cocrystal model with the ratio 3:4:1 is predicted to be the most stable phase. CL-20/HMX/TNAD cocrystal models have higher value of trigger bond energy than pure CL-20 and CL-20/HMX cocrystal models, meaning that the three-component energetic cocrystal is more insensitive. The crystal density and detonation parameters of CL-20/HMX and CL-20/HMX/TNAD cocrystal models are lower than CL-20, illustrating that the energy density is declined. The CL-20/HMX/TNAD cocrystal has higher energy density than RDX and can be regarded as a potential high energy explosive. This paper was performed with molecular dynamics (MD) method with the software of Materials Studio 7.0 under COMPASS force field. The MD simulation was performed under isothermal-isobaric (NPT) ensemble, the temperature and pressure was 295K and 0.0001 GPa, respectively.

Computational Study of 1-(3-Nitrobenzoyloxymethyl)-5-Fluorouracyl Derivatives as Colorectal Cancer Agents

Cancer is one of the chronic diseases with a reasonably high increase at this time. One type of cancer with the highest mortality rate is colorectal cancer. Colorectal cancer is cancer that occurs in the colon and rectum. Based on GLOBOCAN data (2018), cases of colorectal cancer in Indonesia reached 8.6% or 30,017 people and were the second most common cause of death in men and the third in women. The development of cancer drugs to obtain drugs with better activity, lower toxicity, and working more selectively through structural modifications is still being carried out until now. This study aims to determine the pharmacokinetic properties and stable interactions between the thymidylate synthase and one of the 78 derivatives of 1-(3-nitrobenzoiloximethyl)-5-fluorouracyl (NB5FU) by in silico, namely molecular docking, and molecular dynamics simulations. The result shows that the NB5FU78 derivative compounds have better pharmacokinetic properties than NB5FU. Lipinski's rules of five criteria that fill the requirements have a smaller free bond energy value than NB5FU. Based on the results of molecular dynamics simulations carried out for 5 ns, the NB5FU78 derivative has a stable interaction with the thymidylate synthase (TS) receptor with total bond energy of -36.36 kcal/mol.

In silico Study of Essential Oil of Bambusa vulgaris Leaves as an Anti Beta-lactamase Compound

Background: Klebsiella pneumoniae is known as an extended spectrum beta (β)-lactamases (ESBLs)-producing bacteria, which produces enzymes that cause resistance to β-lactam antibiotics by degrading β-lactam ring. A solution is needed to prevent the degradation of the β-lactam ring. In this in silico study, combining β-lactam antibiotics with secondary metabolites has the possibility to inhibit the active site of the β-lactamase enzyme. This study aimed to explore the potential of the essential oil of yellow bamboo (Bambusa vulgaris) leaves as inhibitors of β-lactamase. Materials and methods: This research was conducted by simulating molecular docking to determine the interaction of ligands with proteins, pharmacological tests of compounds based on the Lipinski’s rule of five, and ligand toxicity tests with pkCSM. Results: The free bond energy values (∆G) were in the range of -4.3 to -8.0 kcal/mol. The ligands with the best ∆G value were sulfur pentafluoride (-8.0 kcal/mol), squalene (-7.3 kcal/mol), 3-aminodibenzofuran (-7.1 kcal/mol), and 2- monolaurin (-5.5 kcal/mol). Secondary metabolites from the essential oil of B. vulgaris leaves fulfilled Lipinski’s rule of five, so that oral use can be carried out except for squalene and tridecane. Conclusion: Secondary metabolite compounds in the essential oil that have potential as oral drugs based on the Lipinski pharmacological test and the pkCSM toxicity test are dipivaloylmethane, β-ocimene, 2-monolaurin, and undecane. Keywords: β-lactamase, Bambusa vulgaris, essential oil, Klebsiella pneumoniae

Secang wood (Caesalpinia sappan L.) nanoemulgel activity as antiaging through suppressing the MMP-1 expression and the collagen degradation

Context: Aging is closely related to reactive oxygen species (ROS). ROS increases the collagenase enzyme (MMP-1) levels and collagen degradation that causes skin wrinkling. Secang wood (Caesalpinia sappan L.) containing brazilin and brazilein has been shown to have photoprotective and antioxidant properties. Aims: To evaluate the activity of C. sappan nanoemulgel as antiaging agent against the target protein, matrix metalloproteinases (MMPs), especially MMP-1, MMP-3, and MMP-9 by in silico assay and using in vivo assay through MMP-1 and collagen expression parameter. Methods: C. sappan nanoemulgel was made by mixing the gel base with C. sappan nanoemulsion from heartwood extract. The C. sappan nanoemulsion was formulated using the Self Nanoemulsifying Drug Delivery System method. In vivo testing was conducted with a post-test-only control group design and used male Wistar rats. MMP-1 expression was examined using immunohistochemical techniques, and the amount of dermal collagen was observed with Picro Sirius Red staining. In silico assay using a computational method with Autodock 4.2 program. Results: C. sappan nanoemulgel concentrations of 0.0625, 0.125, and 0.25% obstruct the expression of MMP-1 and collagen degradation. The bond energy value to MMP-1, MMP-3, and MMP-9 were -8.04, -10.40, and -8.70 kcal/mol (for brazilin); -8.82; -10.99, and -8.51 kcal/mol (for brazilein). Conclusions: Nanoemulgel containing C. sappan nanoemulsion has a potential activity as an antiaging agent by repressing MMP-1 expression and dermal collagen degradation. C. sappan nanoemulgel 0.25% showed the best result as antiaging. Brazilin and brazilein from C. sappan inhibit the MMP-1, MMP-3, and MMP-9 by in silico assay.

Adsorptive capacity of a g-C3N4 matrix for thiamethoxam removal: A DFT study

In this study, the adsorptive capacity of the insecticide thiamethoxam (TMX) on a graphitic carbon nitride matrix (g-C3N4) was studied theoretically. Two adsorbent-adsorbate complexes, g-C3N4-TMX1 and g-C3N4-TMX2 was formed through hydrogen bonds (HB) and the the hydrogen bonds lengths ranging from 2.610 Å to 3.538 Å. Topological analyses based on the quantum theory of atoms in molecules confirmed the bond critical points of hydrogen bonds. Further, it allowed for the classification of the HBs as weak, with hydrogen bond energy values ranging from −0.98 to −6.58 kJ mol−1. Calculations of the energies involved in the processes proved that the interaction of TMX with the g-C3N4 matrix occurs in two sites with values of ΔEBind = −71.65 kJ mol−1 and ΔEBind = −70.44 kJ mol−1, sites 1 and 2, respectively. The results showed that the interaction is is spontaneous and exothermic, as indicated by the negative values of ΔG and ΔH.

Molecule Attachment and Prediction of ADMET Compounds in Cinnamomum burmannii on Orexin Receptor as Anti-insomnia

Background and Objectives: Insomnia is a sleep disorder characterized by a person's dissatisfaction with the quantity or quality of sleep. Suvorexant is a sedative and hypnotic drug that has been shown to be useful for the treatment of insomnia and can act more centrally and selectively on the orexin system. However, suvorexant has quite a lot of side effects. According to research, cinnamon has pharmacological benefits, one of which is anti-insomnia. The aimed this study to determine the interaction between the compounds contained in the cinnamon plant and the Orexin receptor with the molecular anchoring method and to determine the prediction of the ADMET properties of cinnamon compounds which have the potential as anti-insomniac. Material and Methods: The research method was in-silico study consisted of validation, bonding of cinnamon compounds and prediction of ADMET properties. Results: The results showed that cinnamon compounds, namely Cinnamic acid and Methylhidroxy calcone, had the best interactions with lower Gibbs bond energy values (ΔG) and inhibition constants (Ki). From the results of the prediction of ADMET properties, the Methylhydroxy calcone compound obtained positive results on the hepatotoxicity parameter and the Cinnamic acid compound obtained negative results, which means that the compound does not have toxic properties. Conclusion: The Cinnamic acid could be used as a new promising anti-insomnia agent.