Argus Lab Research Articles

Isolation, In Silico Design and Anti-Inflammatory Activity of Spirosolenol from the Roots of Solanum anguvi

The aim of our research was the isolation of the steroidal alkaloid glycosides such as anguivine and isoanguivine from the dried roots of S. anguvi and evaluation of their anti-inflammatory activity by HRBC and carrageenan induced paw edema method. The PASS programme predicts the anti-inflammatory activity of the aglycon part of spirosolenol, on the basis of a similarity structure based drug design. Molecular docking studies with human phospholipase A2 enzyme were carried outby utilizing Argus lab 4.0.1.version. The in silico study and pharmacological activity were correlated with good agreement.

Computational molecular docking studies on anticancer drugs

ObjectiveCancer can be described as the uncontrolled growth of abnormal cells. Lung cancer is one of the commonest malignant neoplasms all over the world. Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in non–small–cell lung cancers, representing 2 to 7% of such tumors. ALK proteins play a vital role in deactivating the apoptosis process in cancer disease. Some of the most commonly used non–small–cell lung cancers drugs are Crizotinib, Sunitinibmalate, Tandutinib etc…, Non–small–cell lung cancer Cells need anaplastic lymphoma kinase (ALK) to cell growth and proliferation the role of ALK in malignant proliferation and as a valid drug target. These drugs mainly work against the effects of ALK on these cells. MethodsThe Protein- Ligand interaction plays a significant role in structural based drug designing. In our research work we have taken the Human anaplastic lymphoma kinase (ALK) and the commercially available drugs against non–small–cell lung cancer. The ALK was docked to the above said drugs and the energy value obtained as follows Crizotinib(−9.86), Sunitinib malate(−8.26), Tandutinib(−8.05) using the Argus Lab docking software. ResultsDepending on the energy values we have chosen the best two drugs they are Crizotinib(−9.86) and Sunitinib malate(−8.26). We tried to improve the binding efficiency and steric compatibility of the two drugs namely Crizotinib(−9.86) and Sunitinib malate(−8.26). Several modifications were made to the probable functional groups which were interacting with the receptor molecule. Analogs of this drug molecule were prepared using ACD ChemSketch and docked using Argus Lab docking software. ConclusionsCrizotinib Analog 2 and Sunitinib malate analog 1 were detected with significant energy values and probable lead molecules. The Modified drugs was sketched using Chemsketch were found to be better than the conventional drugs available. Further from this work we can improve the steric compatibility and then ADME/T properties of the Analogs can be analyzed using Inslico ADME/T tools available.

Investigations on Binary Mixtures of Propan-2-ol with Methyl Benzoate and Ethyl Benzoate

The molecular interactions between the polar systems propan-2-ol with alkyl benzoates (methyl benzoate and ethyl benzoate), for various mole fractions and different temperatures, were studied by determining the dielectric permittivity using a LF impedance analyzer and Abbe’s refractometer in the static and optical frequency regions, respectively. The effective Kirkwood correlation factor, corrective Kirkwood correlation factor, dipole moment, excess dipole moment, and excess Helmholtz free energy were calculated using the experimental data. Hamiltonian quantum mechanical calculations (ab initio and semiempirical) were performed using PC Spartan and Argus lab Modeling software for both pure and equimolar binary systems of propan-2-ol with alkyl benzoates.

Molecular Docking Studies of Antimalarial Drugs for Malaria

Malaria is the most important parasitic disease in humans, with transmission occurring in over 100 countries with a population of three billion people. It is caused by protozoan parasites of the genus Plasmodium. These parasites are transmitted from one person to another by the female anopheles mosquito. Proguanil is a prophylactic antimalarial drug, it stops the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. It does this by inhibiting the enzyme, dihydrofolate reductase. The side effects of these drugs make the need for the necessity of new improved drugs Conformational analysis and geometry optimization of Proguanil was performed using Argus Lab & Hex software. When the receptor (DHFR) was docked with the drug Proguanil the energy value obtained was (-6.59) using Argus Lab and (-174.54) using hex. The most feasible position for the drug to interact with the receptor was found to be with analog 2 having energy -9.56 K.cal/mole using Argus Lab and -201.92 K.cal/mole using HEX Tool. So Proguanil Analog 2 sketched using Chemsketch is detected with more signifi cant energy values in both softwares and probable lead molecules. Further from ADME/T properties of the Analogs is also showing the better result than available drug.

English

Interleukin-2 (IL-2) is an immunoregulatory cytokine whose biological effects are mediated through interaction with specific receptors on the surface of target cells. Due to its presumed role in generating a normal immune response, IL-2 is being evaluated for the treatment of a variety of tumors, in addition to infectious diseases. Main drawback of human IL-2 is that the molecule is relatively unstable. Therefore, with the objective of increasing the stability of the molecule, site directed mutagenesis of human IL-2 gene was carried out. Early studies indicated that mutations at three Cysteine residues (58, 105, 125) which are in the active sites of human IL-2 resulted in the reduced stability as well as the biological activity of the molecule. Therefore, mutations were carried out at the positions of amino acid other than the receptor binding sites at 111Valine to Arginine, 117Lysine to Glutamine and 133 Threonine to Asparagine of the human sequence by comparing it with the bovine sequence which has higher stability than the human counterpart, using SWISS PDB tool. To understand the biological activity of the mutated IL-2, energy minimization studies were carried out using SWISS-PDB. Docking studies were performed to check the reliability of the results using HEX DOCK, ARGUS LAB and PATCH DOCK between the IL-2 receptor and its mutated Ligand. These docking results also confirmed that the reliability of these mutated IL-2 gene. Stability, half life and ADME characteristics of these mutants can be studied in a detailed manner in the in

Peptidomimetics Based Inhibitor Design for HIV – 1 gp120 Attachment Protein

Peptidomimetics is a novel drug designing strategy in which an Insilico inhibitor is designed by mimicking the framework of a short peptide. Novel drug design str ate- gies shall only pave way for developing unique and safer anti-HIV drugs. In the present study, we propose a Peptidomimetics based gp120 attachment inhibitor. I n human biological system, HIV-1 interacts with CD4 r e- ceptor of the host via its surface glycoprotein gp1 20 es- tablishing initial attachment. This protein–protein inter- action interface forms the base to derive an inhibi tor mim- icking backbone of the receptor. The mimicked inhib itor derived in this study is based on the insilico interactions of soluble CD4 (SCD4) (precursor of CD4) with gp120 . The molecular interactions of SCD4 with gp120 were iden- tified by MEDock software. Furthermore, the interac ting interface was analyzed manually for topology, and t he backbone of the ligand molecule was sketched based on it with chemsketch. Moreover, the sketched ligand was op- timized and was docked with gp120 using Argus lab. Dock- ing results show six hydrogen bonds formation betwe en the ligand and binding interface of gp120. The liga nd was also found to be fit with good druggable character, as per Lipinski’s rule of five. Hence, this work addresses the drug likeness of the peptidomimetic ligand proposed.

Conformational and microwave dielectric relaxation studies of hydrogen bonded polar binary mixtures of propionaldehyde with isopropyl amine

The dielectric behaviour of the polar liquids like propionaldehyde, isopropyl amine and their equimolar binary mixture in nonpolar solvent benzene is studied in the microwave frequency range using the cavity perturbation technique at 6.218 GHz (J band), 9.880 GHz (X band), 16.331 GHz (P band) and 24.951 GHz (K band). Hamiltonian quantum mechanical calculations such as AM1, PM3, and MNDO optimized converged geometry operation is performed by using Argus lab chemical modelling software 2004 for both pure and binary systems of propionaldehyde and isopropyl amine. Dipole moments of the binary mixtures are calculated from the dielectric data using Higasi's method and compared with the theoretical results. Conformational analysis of the formation of a hydrogen bond between the propionaldehyde and isopropyl amine is supported by FT-IR, proton NMR spectra and molecular polarizability calculations. The average relaxation times are calculated from their respective Cole–Cole plots.

Microwave dielectric absorption studies of hydrogen bonded polar binary mixtures of isobutanol with tertiary butyl amine

The dielectric behaviour of polar liquids like isobutanol, tertiary butyl amine and their equimolar binary mixture in nonpolar solvent benzene is studied in the microwave frequency range using the cavity perturbation technique at 6.218 GHz (J band), 9.880 GHz (X band), 16.331 GHz (P band) and 24.951 GHz (K band). Hamiltonian quantum mechanical calculations such as AM1, PM3 and MNDO optimized converged geometry operation is performed on isobutanol, tertiary butyl amine and their equimolar binary mixtures using Argus lab chemical modelling software, 2004. Dipole moments of the binary mixtures are calculated from the dielectric data using Higasi's method, and compared with the theoretical Hamiltonian quantum mechanical results. Conformational analysis of the formation of hydrogen bond between the isobutanol and tertiary butyl amine is supported by FT-IR and proton NMR spectra. The average relaxation times are calculated from their respective Cole–Cole plots.

Conformational and dielectric analysis of hydrogen bonded polar binary mixtures of propan-1-ol with isopropyl amine

The dielectric behavior of the polar liquids like propan-1-ol, isopropyl amine and their equimolar binary mixture in nonpolar solvent benzene is studied in the microwave frequency range using the cavity perturbation technique at 6.218 GHz (J band), 9.880 GHz (X band), 16.331 GHz (P band) and 24.951 GHz (K band). Hamiltonian quantum mechanical calculations such as AM1, PM3, and MNDO optimized converged geometry operation is performed by using Argus lab chemical modeling software 2004 for both pure and binary system of propan-1-ol and isopropyl amine. Dipole moments of the binary mixtures are calculated from the dielectric data using Higasi’s method and compared with the theoretical results. Conformational analysis of the formation of hydrogen bond between the propan-1-ol and isopropyl amine is supported by the FT-IR and proton NMR spectra. The average relaxation times are calculated from their respective Cole–Cole plots.