Supramolecular Chemistry of Bile Acid Derivatives: Formation of Gels

This article describes some of the exciting results obtained during the study of the gelation behavior of bile acid derivatives in the authors laboratory. The serendipitous discovery of charge-transfer interaction promoted gelation of organic solvents by (steroid)pyrene derivatives/TNF is presented. In this class of molecules, the effect of the location of the chiral center in chiral gelators on the overall chirality of the aggregates in the gel was studied. Also described are the aggregation behavior of bile acid based aqueous gelators which led us to postulate design principals to obtain bile acid based aqueous/organogelators.     

Hamilton Cycle Rich 2-Factorization of Complete Equipartite Graphs-II

For any given two 2-factors G and H of a complete p-partite graph K(m, p), with m vertices in each partite set, we prove the existence of a 2-factorization of K(m, p), in which one 2-factor is isomorphic to G, another 2-factor is isomorphic to H and the remaining 2-factors are hamilton cycles. Further, we prove the corresponding result for K(m, p) ? I, where I is a 1-factor of K(m, p), when K(m, p) is an odd regular graph. In fact our results together with the results of McCauley and Rodger settled the problem of 2-factorization of K(m, p), when two of the 2-factors are isomorphic to the given two 2-factors and the remaining 2-factors are hamilton cycles except for (m, p)?=?(m, 2).     

Effects of aqueous extracts of Acacia albida stem bark on Wistar albino rats infected with Trypanosoma evansi

The effect of aqueous extract of Acacia albida stem bark was investigated in Wistar albino rats infected with Trypanosoma evansi. The extract showed highest reduction in parasitemia at the dose of 600 mg/kg body weight (bw). A dose of 300 mg/kg bw improved packed cell volume the most by 14.35%. The group treated with 150 and 600 mg/kg bw of the extract showed significant decrease (P < 0.05) in alanine transaminase and aspartate transaminase levels which were lower than those of the group treated with diminazene aceturate. The group treated with 150 mg/kg bw of the extract showed the least urea, albumin and protein level and lowest relative organ weight. There was a significant difference (P < 0.05) in the levels of catalase and Thiobarbituric acid reactive substances in liver and kidney of the animals in the infected-untreated group and the extracts-treated groups. The results of this study show that the extracts of A. albida have antitrypanosomal activity against T. evansi infection.     

Micellization of Metallosurfactant N-Dodecyl/Hexadecyl/Octadecyl Salicylaldimine Cobalt(III) Complexes in Nonaqueous Media

Abstract The critical micelle concentrations (CMC) of three metallosurfactant Schiff base cobalt(III) complexes of the type [Co(trien)(C₁₉H₃₀NO)]Cl₂,[Co(trien) (C₂₃H₃₈NO)]Cl₂ and [Co(trien)(C₂₅H₄₂NO)]Cl₂, where trien = triethylenetetramine, have been studied in n-alcohol and in formamide at different temperatures by the electrical conductivity method. CMCs have also been measured as a function of percentage concentration of alcohol in the mixed solvents with formamide. Specific conductivity data (at 303–323 K) served for the evaluation of the temperature-dependent CMC and thermodynamic parameters such as the standard Gibbs energy changes (DG^°_mic)\Delta G^{\circ}_{\mathrm{mic}}), enthalpy changes (DH^°_mic)\Delta H^{\circ}_{\mathrm{mic}}), and entropy changes (DS^°_mic)\Delta S^{\circ}_{\mathrm{mic}}) of micelle formation. It is suggested that addition of an alcohol leads to increased penetration of formamide into the micellar interface, the extent depending on the alcohol’s chain length. The results have been discussed in terms of the solvophobic interaction, dielectric constant of the medium, the chain length of the alcohol, and the surfactant in the solvent mixture.     

Optimization of hole shapes in circular cylindrical shells under axial tension

Hole shapes are optimized in circular cylindrical shells subjected to axial load considering only the predominantly large membrane stresses present around the holes. Two-dimensional photoelastic isochromatics obtained with a special-purpose polariscope are utilized for the optimization process. The process leads to a significant decrease in the membrane stress-concentration factor and a modest decrease in weight, thus yielding a considerable increase in strength-to-weight ratio. This paper presents results for certain typical ratios of hole diameter to shell diameter. Previous theoretical and experimental studies for the circular hole have also been verified     

Click activated protodrugs against cancer increase the therapeutic potential of chemotherapy through local capture and activation

A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The CAPAC platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans-cyclooctene (TCO)-modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels–Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapies. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies. In mice, the maximum tolerated dose (MTD) of SQP33 in combination with locally injected tetrazine-modified biopolymer (SQL70) was determined to be 19.1-times the MTD of conventional doxorubicin. Pharmacokinetics studies in rats show that a single injection of SQL70 efficiently captures multiple SQP33 protodrug doses given cumulatively at 10.8-times the MTD of conventional doxorubicin with greatly reduced systemic toxicity. Finally, combined treatment with SQL70 and SQP33 (together called SQ3370) showed antitumor activity in a syngeneic tumor model in mice.

The Click Activated Protodrugs Against Cancer (CAPAC) platform uses click chemistry to activate cytotoxic drugs directly at a target site with minimal toxicity, overcoming limitations of conventional chemotherapy and traditional targeted therapies.     

Cloning, characterization, and expression of a new cry2Ab gene from Bacillus thuringiensis strain 14-1

Bacillus thuringiensis is the major source for transfer of genes to impart insect resistance in transgenic plants. Cry2A proteins of B. thuringiensis are promising candidates for management of resistance development in insects owing to their difference from the currently used Cry1A proteins, in structure and insecticidal mechanism. The cry2Ab gene was found to lack a functional promoter and, hence, is cryptic in nature. The cry2Ab7 gene was cloned from a new indigenous B. thuringiensis strain, 14-1. Nucleotide sequencing of the cry2Ab gene cloned from B. thuringiensis strain 14-1 revealed an open reading frame of 1902 bp. The deduced amino acid sequence of Cry2Ab of B. thuringiensis strain 14-1 showed a variation in three amino acid residues in comparison to the holotype sequence, Cry2Ab1. Expression of the newly cloned cry2Ab gene was studied in an acrystalliferous strain of B. thuringiensis (4Q7) by fusing the cry2Ab gene downstream of cry2Aa promoter and orf1+orf2 sequences. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of a spore-crystal mixture obtained from transformants of B. thuringiensis strain 4Q7 showed production of Cry2Ab protein of about 65 kDa. Alkali solubilized Cry2Ab7 protein showed toxicity against Helicoverpa armigera neonates.