Design, synthesis and molecular docking studies of new azomethine derivatives as promising anti-inflammatory agents.

Herein, we synthesized a series of Ibuprofen-based 4a-k, quinoxaline-based 9a-f and pyridine-based 13a-h azomethine derivatives and studied their anti-inflammatory potency. The in-silico docking studies of the synthesized compounds 4a-k revealed better affinity for COX-2 as compared to COX-1 with best binding exhibited by 4a, 4d, and 4k.In vitro COX-1 and COX-2 inhibition assay performed on the azomethine derivatives further proved that synthesized compounds of series 4, 9 and 13 showed less inhibition of COX-1 enzyme than that of COX-2 enzyme.

Assessment of elementary derivatives of 1,5-benzodiazepine as anticancer agents with synergy potential.

Herein, we designed and synthesized 1,5-benzodiazepines as a lead molecule for anticancer activity and as potent synergistic activity with drug Methotrexate. Working under the framework of green chemistry principles, series of 1,5-benzodiazepine derivatives (3a-3a) were synthesized using biocatalyst i.e.

Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation.

Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE).

Material And Methods: Three cyclodextrins: β-cyclodextrin (BCD), hydroxypropyl-β-cyclodextrin (HPBCD) and Sulfobutylether-7-β-cyclodextrin (SBEBCD) were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation.

Physical basis for the ofloxacin-induced acceleration of lysozyme aggregation and polymorphism in amyloid fibrils.

Aggregation of globular proteins is an intractable problem which generally originates from partially folded structures. The partially folded structures first collapse non-specifically and then reorganize into amyloid-like fibrils via one or more oligomeric intermediates. The fibrils and their on/off pathway intermediates may be toxic to cells and form toxic deposits in different human organs.

Effects of 2-amino-8-hydroxyquinoline interaction on the conformation of physiological isomers of human serum albumin.

The methods of synthetic chemistry create small molecules rapidly for screening, and ligand-protein interaction studies provide information on how a potential drug interacts with target or carrier proteins such as serum albumin. In this work, we investigate the interaction of amino derivative of 8-hydroxyquinoline, 2-amino-8-hydroxyquinoline (A8HQ), and the effects of its binding on the conformation of different isomers of human serum albumin (HSA) using multispectroscopic techniques and molecular modeling. We found that B isomer, which exists at pH 9, bound A8HQ (K a = 1.

Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?

Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation.

Targeting dormant tuberculosis bacilli: results for molecules with a novel pyrimidone scaffold.

Our inability to completely control TB has been due in part to the presence of dormant mycobacteria. This also renders drug regimens ineffective and is the prime cause of the appearance of drug-resistant strains. In continuation of our efforts to develop novel antitubercular agents that especially target dormant mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and subsequently tested against both the dormant and virulent BCG strain of M.

Quantifying ligand-receptor interactions for gorge-spanning acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.

There is a need for continued development of acetylcholinesterase (AChE) inhibitors that could prolong the life of acetylcholine in the synaptic cleft and also prevent the aggregation of amyloid peptides associated with Alzheimer's disease. The lack of a 3D-QSAR model which specifically deconvulates the type of interactions and quantifies them in terms of energies has motivated us to report a CoRIA model vis-à-vis the standard 3D-QSAR methods, CoMFA and CoMSIA. The CoRIA model was found to be statistically superior to the CoMFA and CoMSIA models and it could efficiently extract key residues involved in ligand recognition and binding to AChE.

Valsartan inclusion by methyl-β-cyclodextrin: thermodynamics, molecular modelling, Tween 80 effect and evaluation.

The rationale of present study is to investigate the effect of Tween 80 on encapsulation ability of valsartan (VAL) by methyl-β-cyclodextrin (M-β-CD) and to determine the exact mode of binding. Phase solubility studies indicated 1:1 stoichiometry between VAL and M-β-CD both in the presence and absence of Tween 80. The NMR and molecular modelling studies indicated the insertion of both aromatic and aliphatic regions of VAL into the M-β-CD cavity suggesting the coexistence of two 1:1 complexes in equilibrium with each other.

Curcumin and kaempferol prevent lysozyme fibril formation by modulating aggregation kinetic parameters.

Interaction of small molecule inhibitors with protein aggregates has been studied extensively, but how these inhibitors modulate aggregation kinetic parameters is little understood. In this work, we investigated the ability of two potential aggregation inhibiting drugs, curcumin and kaempferol, to control the kinetic parameters of aggregation reaction. Using thioflavin T fluorescence and static light scattering, the kinetic parameters such as amplitude, elongation rate constant and lag time of guanidine hydrochloride-induced aggregation reactions of hen egg white lysozyme were studied.

Telmisartan complex augments solubility, dissolution and drug delivery in prostate cancer cells.

Telmisartan (TEL) requires superior bioavailability in cancer cell compartments. To meet these challenges, we have synthesized a 2-HP-β-CD-TEL complex with stability constant (Kc) of 2.39 × 10(-3)mM.

HomoSAR: bridging comparative protein modeling with quantitative structural activity relationship to design new peptides.

Peptides play significant roles in the biological world. To optimize activity for a specific therapeutic target, peptide library synthesis is inevitable; which is a time consuming and expensive. Computational approaches provide a promising way to simply elucidate the structural basis in the design of new peptides.

Design, synthesis, structural characterization by IR, (1) H, (13) C, (15) N, 2D-NMR, X-ray diffraction and evaluation of a new class of phenylaminoacetic acid benzylidene hydrazines as pfENR inhibitors.

Recent studies have revealed that plasmodial enoyl-ACP reductase (pfENR, FabI), one of the crucial enzymes in the plasmodial type II fatty acid synthesis II (FAS II) pathway, is a promising target for liver stage malaria infections. Hence, pfENR inhibitors have the potential to be used as causal malarial prophylactic agents. In this study, we report the design, synthesis, structural characterization and evaluation of a new class of pfENR inhibitors.

Interaction of multimicrobial synthetic inhibitor 1,2-bis(2-benzimidazolyl)-1,2-ethanediol with serum albumin: spectroscopic and computational studies.

The molecule, 1,2-Bis(2-benzimidazolyl)-1,2-ethanediol (BBE) is known to act as a selective inhibitor of poliovirus, rhinovirus, Candida albicans, several bacterial species, and is easily synthesized by Phillips reaction. The interaction of BBE with BSA and the effects of its binding on the conformation and unfolding/refolding pathways of the protein were investigated using multispectroscopic techniques and molecular modeling. The binding studies indicate that BSA has one high affinity BBE binding site with association constant 6.

Sulfobutyl ether(7) β-cyclodextrin (SBE(7) β-CD) carbamazepine complex: preparation, characterization, molecular modeling, and evaluation of in vivo anti-epileptic activity.

The objective of the present investigation was to study the ability of sulfobutyl ether(7)-β-cyclodextrin to form an inclusion complex with carbamazepine, an anti-epileptic drug with poor water solubility. The formation of the complex was carried out using the industrially feasible spray-drying method. The inclusion complex and physical mixtures were characterized by various techniques such as differential scanning calorimetry (DSC), infrared (IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and molecular modeling.

Interaction of artesunate with β-cyclodextrin: Characterization, thermodynamic parameters, molecular modeling, effect of PEG on complexation and antimalarial activity.

Inclusion of artesunate in the cavity of β-cyclodextrin (β-CD) as well as its methyl and hydroxypropyl derivatives was investigated experimentally and by molecular modeling studies. The effect of PEG on the inclusion was also studied. A 1:1 stoichiometry was indicated by phase-solubility studies both in the presence and absence of PEG and suggested by the mass spectrometry.

Ensemble QSAR: a QSAR method based on conformational ensembles and metric descriptors.

Quantitative structure-activity relationship (QSAR) is the most versatile tool in computer-assisted molecular design. One conceptual drawback seen in QSAR approaches is the "one chemical-one structure-one parameter value" dogma where the model development is based on physicochemical description for a single molecular conformation, while ignoring the rest of the conformational space. It is well known that molecules have several low-energy conformations populated at physiological temperature, and each conformer makes a significant impact on associated properties such as biological activity.

Mapping interactions of gastric inhibitory polypeptide with GIPR N-terminus using NMR and molecular dynamics simulations.

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide, or GIP), a 42-amino acid incretin hormone, modulates insulin secretion in a glucose-concentration-dependent manner. Its insulinotropic action is highly dependent on glucose concentration that surmounts the hypoglycemia side effects associated with current therapy. In order to develop a GIP-based anti-diabetic therapy, it is essential to establish the 3D structure of the peptide and study its interaction with the GIP receptor (GIPR) in detail.

Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines.

In continuation of our research program on new antitubercular agents, this article is a report of the synthesis of 97 various symmetrical, unsymmetrical, and N-substituted 1,4-dihydropyridines. The synthesized molecules were tested for their activity against M. tuberculosis H (37)Rv strain with rifampin as the standard drug.

Molecular modeling studies, synthesis, and biological evaluation of Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) inhibitors.

The search for new antimalarial agents is necessary as current drugs in the market become vulnerable due to the emergence of resistance strains of Plasmodium falciparum (P. falciparum). The biosynthetic pathway for fatty acids has been recognized and validated as an important drug target in P.

Synthesis, screening for antitubercular activity and 3D-QSAR studies of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxamides.

Multi-drug resistance to commonly used antitubercular drugs has propelled the development of new structural classes of antitubercular agents. This paper reports the synthesis, evaluation and 3D-QSAR analysis of a set of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamides as antitubercular agents. Substituted acetoacetanilides were reacted with various aromatic aldehydes and urea which yielded the tetrahydropyrimidine derivatives with a phenyl carbamoyl group at C5 position, and with various substitutions on the 4-phenyl and the N-phenyl aromatic rings.

3D-QSAR studies of Dipeptidyl peptidase IV inhibitors using a docking based alignment.

Dipeptidyl peptidase IV (DPP-IV) deactivates the incretin hormones GLP-1 and GIP by cleaving the penultimate proline or alanine from the N-terminal (P1-position) of the peptide. Inhibition of this enzyme will prevent the degradation of the incretin hormones and maintain glucose homeostasis; this makes it an attractive target for the development of drugs for diabetes. This paper reports 3D-QSAR analysis of several DPP-IV inhibitors, which were aligned by the receptor-based technique.

Furo-fused BINOL based crown as a fluorescent chiral sensor for enantioselective recognition of phenylethylamine and ethyl ester of valine.

A furo-fused BINOL based chiral crown was developed as an enantioselective chiral sensor for phenylethylamine and ethyl ester of valine. Fusion of furan to BINOL has resulted in a highly stereo-discriminating backbone for the chiral crown developed. This chiral crown exhibited a fluorescence enhancement difference of 2.