Synthesis of biologically active cefpodoxime and vanillin-based schiff base metal complexes with the detailed biological evaluations.

Schiff bases of existing antimicrobial drugs are an area, which is still to be comprehensively explored to improve drug efficiency against consistently resisting bacterial species. In this study, we have targeted a new and eco-friendly method of condensation reaction that allows the "green synthesis" as well as improved biological efficacy. The transition metal complexes of cefpodoxime with well-enhanced biological activities were synthesized. The condensation reaction product of cefpodoxime and vanillin was further reacted with suitable metal salts of [Mn (II), Cu (II), Fe (II), Zn (II), and Ni (II)] with 1:2 molar ratio (metal: ligand). The characterization of all the products were carried out by using UV-Visible, elemental analyzer, FTIR, 1H-NMR, ICP-OES, and LC-MS. Electronic data obtained by UV-Visible proved the octahedral geometry of metal complexes. The biological activities Schiff base ligand and its transition metal complexes were tested by using in-vitro anti-bacterial analysis against various Gram-negative, as well as Gram-positive bacterial strains. Proteinase and protein denaturation inhibition assays were utilized to evaluate the products in-vitro anti-inflammatory activities. The in vitro antioxidant activity of the ligand and its complexes was evaluated by utilizing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) in-vitro method. The final results proved metal complexes to be more effective against bacterial microorganisms as compared to respective parent drug as well as their free ligands. Patch Dock, a molecular docking tool, was used to dock complexes 1a-5e with the crystal structure of GlcN-6-P synthase (ID: 1MOQ). According to the docking results, complex 2b exhibited a highest score (8,882; ACE = -580.43 kcal/mol) that is well correlated with a high inhibition as compared to other complexes which corresponds to the antibacterial screening outcomes.

Synthesis, spectroscopic characterization, molecular docking and theoretical studies (DFT) of N-(4-aminophenylsulfonyl)-2-(4-isobutylphenyl) propanamide having potential enzyme inhibition applications.

A mutual prodrug (1) of ibuprofen and sulphanilamide has been synthesized with dual activity and improved toxicity profile. The synthesized compound has been characterized by elemental analysis, FT-IR, 1HNMR, 13CNMR and ESI-MS. The molecular geometry of the compound (1) was optimized using density functional theory (DFT/B3LYP) method with the 6-311G(d,p) basis sets in ground state. Geometric parameters (bond lengths, bond angles, torsion angles), vibrational assignments, chemical shifts and thermodynamics of the compound (1) has been calculated theoretically and compared with the experimental data. Comparative AutoDock study of compound (1) with cyclooxygenase enzymes (COX-1 and COX-2) were performed involving docking for possible selectivity of our prodrug within the two Cox enzymes. The highest binding affinities of -8.7 Kcal/mol and -8.1 Kcal/mol has been obtained for COX-1 and COX-2 enzymes respectively. Compound (1) exhibited enhanced anti-inflammatory, anti-ulcer and free radical scavenging activities as compared with the parent drugs. Based on various in vitro and in vivo tests it is suggested that the Compound (1) is more active than the parent drugs. Moreover, LD50 of compound (1) is higher than parent drug i.e. ibuprofen and sulphanilamide suggesting that the synthesized compound is much safer than its parent analogous.

Optimization of process variables for increased production of lovastatin in Aspergillus terreus PU-PCSIR1 and its characterization.

During intrinsic cholesterol formation 3-hydroxy-3-methylgutaryl coenzyme A reductase (HMGCR) converts HMGCoA to mevalonate, in biosynthetic cascade of cholesterol. Statins, competitive inhibitors of HMGCR, now-a-days commonly used to lower the blood-cholesterol level in the hyper-cholesterolemic patients. Lovastatin, one of the most potent natural statins, was produced from wild-type indigenous isolate Aspergillus terreus PU-PCSIR-1, through solid state fermentation (SSF). This study was carried out to investigate different parameters influencing lovastatin production such as pH, carbon source, nitrogen source and media components etc. Each parameter was investigated separately to optimize lovastatin production. Maximum yield of 2860mg/Kg of total lovastatin, comprising 1700 and 1160mg/Kg of hydroxy and lactone forms respectively, was achieved after incubating for 14 days, pH 5.5 and at 28°C. The integrity of biotechnologically-produced lovastatin was analyzed using high performance liquid chromatography (HPLC). Lovastatin was purified by preparative HPLC, and was characterized by FT-IR and LC-MS analyses. The study revealed that A. terreus PU-PCSIR-1 has been proved to be a potent strain for the production of lovastatin that has great pharmaceutical and commercial applications.

Stereoselective preparation of lipidated carboxymethyl-proline/pipecolic acid derivatives via coupling of engineered crotonases with an alkylmalonyl-CoA synthetase.

The trisubstituted enolate- and C-C bond-forming capacities of engineered carboxymethylproline synthases CMPSs are coupled with the malonyl-CoA synthetase MatB to enable stereoselective preparation of 5- and 6-membered N-heterocycles functionalised with alkyl-substituted carboxymethyl side chains, starting from achiral alkyl-substituted malonic acids and L-amino acid semialdehydes. The results illustrate the biocatalytic utility of crotonases in tandem enzyme-catalysed reactions for stereoselective synthesis.

Synthesis, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities, and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide.

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows ∼2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and ∼1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of -12.9 kcal mol-1 and -9.8 kcal mol-1 respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be -10.1 kcal mol-1 and -8.9 kcal mol-1, respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver-Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer's disease. Moreover, compound (1) also exhibit better α-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds.

Mutual prodrug of cephazolin and benzydamin: 3-[(1-benzyl-1H-indazol-3-yl)-oxy]-N,N-dimethyl-propan-1-aminium 3-{[(5-methyl-1,3,4-thia-diazol-2-yl)sulfan-yl]meth-yl}-8-oxo-7-[(1H-tetra-zol-1-yl)acetamido]-5-thia-1-aza-bicyclo-[4.2.0]octane-2-carboxyl-ate (benzydaminium cephazolinate).

In the crystal of the title mol-ecular salt, C(19)H(24)N(3)O(+)·C(14)H(13)N(8)O(4)S(3) (-), the cations and anions are linked by N-H⋯O hydrogen bonds. Short intra-molecular C-H⋯O contacts occur within the anion and inter-molecular C-H⋯O and C-H⋯π bonds help to establish the packing.