A Novel Docetaxel-Biotin Chemical Conjugate for Prostate Cancer Treatment

A novel conjugate of docetaxel and biotin (designated as IDD-1010) was designed and chemically synthesized via an ester linkage at position 2’ carbon in docetaxel. The synthesized pure IDD-1010 exhibits a potent anti-cancer activity in in vitro and in vivo studies. At 10 nM, IDD-1010 has induced increased apoptosis and mitotic arrest of PC3-Luc prostate cancer cells, causing aneuploidy and cell death at higher concentrations. Toxicology studies indicate that the maximal tolerated dose (MTD) of IDD-1010 is 150 mg/kg in mice; equivalent to about 12.2 mg/kg of body weight, or to about an 850 mg dose for a patient weighing 70 kg. The MTD-treated mice exhibited weight gain similar to that of the control group, with no gross pathological signs at 14 days post-dosing. At a lower dose, IDD-1010 treatment did not lead to any significant weight loss in mice, although decreased the tumor volume stemming from injecting cancer cells into the dorsal loop of mouse prostate, and it was found to be more potent than Paclitaxel (reference drug). Similarly, IDD-1010 treatment significantly reduced tumor weight and thereby increased the percentage of mice survival as compared to reference drug-treated and control groups. To summarize, the described experiments using IDD-1010, as compared to the reference drug, strongly suggest a potential treatment utility with a wider therapeutic window for prostate cancer. Henceforth, clinical research on such a novel drug candidate would be greatly worthwhile.     

On the wake of a circular cylinder with nodal and saddle attachment

Flow field of a cylinder with a mid-span curvature was experimentally investigated in a wind tunnel and a water tunnel. The azimuthal orientation of the cylinder was changed to obtain a nodal, saddle and a mixed nodal–saddle type of flow attachment. Surface flow topology suggested that the nature of the attachment strongly influenced the spanwise distributions of foci structures that play a significant role in introducing three-dimensionality in the immediate wake. Flow visualization in the water tunnel revealed that the length of a vortex formation region also followed the changes in the nature of the attachment. A symmetric shedding of vortices was observed with a saddle type of attachment. Wake mean velocity profiles showed that the velocity defect and therefore the drag of a curved cylinder was minimum for nodal, and maximum for saddle type of attachment. Nomenclature of the wake was compared with asymptotic profiles and equilibrium parameters. Approach to self-preservation, similarity and other features are discussed.     

Simultaneous determination of ofloxacin,tetrahydrozoline hydrochloride,and prednisolone acetate by high-performance liquid chromatography

A simple, specific, and precise high-performance liquid chromatographic method has been developed for the simultaneous determination of ofloxacin (OFX), tetrahydrozoline hydrochloride (THC), and prednisolone acetate (PAC) in ophthalmic suspension using propylparaben (POP) as the internal standard. The mobile phase consists of 0.05 M phosphate buffer-acetonitrile (65:35, v/v), and the pH is adjusted to 2.7 with orthophosphoric acid. A column containing octadecyl silane chemically bonded to porous silica particles (Waters Spherisorb, 5 microm ODS 1, 4.6 x 150 mm) is used as the stationary phase. The detection is carried out using a variable wavelength UV-vis detector set at 210 nm for OFX and THC and 254 nm for POP (internal standard) and PAC. The solutions are chromatographed at a constant flow rate of 1.2 mL/min. Retention times for OFX, THC, POP, and PAC are approximately 2.5, 4.5, 7.8, and 9.5 min, respectively. The relative retention times are approximately 0.14 min for OFX, 0.35 min for THC, 1.00 min for POP, and 1.22 min for PAC. The linearity range and percent recoveries for OFX, THC, and PAC are 24-120, 4-16, and 16-80 microg/mL and 100.48%, 100.34%, and 100.21%, respectively.     

新疆阿拉山口地区鼠类群落物种多样性的初步研究

根据阿拉山品地区环境和鼠类分布的差异将该地区的鼠类划分为５种鼠类群落，（１）红尾沙鼠＋五趾跳鼠群落，（２）五趾跳鼠＋小家鼠群落；（３）红尾沙鼠群落；（４）褐家鼠＋小家鼠群落；（５）小家鼠＋灰仓鼠群落，同时对鼠类群落的多样性－均匀度和相似性等进行了初步分析。     

Superconductivity in Sr<Subscript>0.75</Subscript>Y<Subscript>0.75</Subscript>Ba<Subscript>1.5</Subscript>Cu<Subscript>3</Subscript> O<Subscript>7−<Emphasis Type="Italic">d</Emphasis></Subscript> compounds

The effect of simultaneous Sr substitution at the Ba and Y sites has been studied in the Sr_0.75Y_0.75Ba_1.5Cu₃O_7–dsystem. Attempts to replace 25% Y and 25% Ba have been successful and superconductivity was observed above 78 K for Sr_0.75Y_0.75Ba_1.5Cu₃O_7–d compound with high oxygen content, i.e., O_6.76, and having orthorhombic crystal symmetry. The compound was treated in argon gas at 800°C to reduce the oxygen content and to induce some structural changes. The Sr_0.75Y_0.75Ba_1.5Cu₃O_6.1 compound thus obtained has tetragonal symmetry and low oxygen content, O_6.1. It has also shown superconductivity at 28 K. The paper presents a careful comparison of the structural and electrical properties and infrared absorbance spectra of the two compounds with the same metallic composition, Sr_0.75Y_0.75Ba_1.5Cu₃, but with different oxygen content and crystal symmetry. The study clearly establishes the occurrence of superconductivity in tetragonal Sr-substituted (both at Y and Ba sites in) YBCO.     

An approach to developing a force field for molecular simulation of martensitic phase transitions between phases with subtle differences in energy and structure

d,l-Norleucine is one of only a few molecules whose crystals exhibit a martensitic or displacive-type phase transformation where the emerging phase shows a topotaxial relationship with the parent phase. The molecular mechanism for such phase transformations, particularly in molecular crystals, is not well understood. Crystalline phases that exhibit displacive phase transitions tend to be very similar in structure and energy. Consequently, the development of a force field for such phases is challenging as the phase behavior is determined by subtle differences in their lattice energies and entropies. We report an approach for developing a force field for such phases with an application to d,l-norleucine. The proposed procedure includes calculation of the phase diagram of the crystalline phases as a function of temperature to identify the best force field. d,l-Norleucine also presents an additional problem since in the solid state it exists as a zwitterion that is unstable in vacuo and therefore cannot be characterized using high-level ab initio calculations in the gas phase. However, a stable zwitterion could be obtained using Onsager's reaction-field continuum model for a solvent (SCRF) using both Hartree-Fock and density functional theory. A number of force fields and the various sets of partial charges obtained from the SCRF calculations were screened for their ability to reproduce the crystal structures of the two known phases, alpha and beta, of d,l-norleucine. Selected parameter sets were then employed in free energy minimizations to identify the best set on the basis of a correct prediction of the alpha-beta phase transition. The Williams' nonbonded parameters combined with partial charges from SCRF-Polarized Continuum Model calculation were found to reproduce the structures of the phases accurately and also maintained their stability in extended molecular dynamics simulations in the Parrinello-Rahman constant stress ensemble. Moreover, we were also able to successfully simulate the phase transformation of the beta- to the alpha-phase. The identified force field should enable detailed studies of the phase transformations exhibited by crystals of d,l-norleucine and hence enhance our understanding of martensitic-type transformations in molecular crystals.     

Pyrrolidinones derived from (S)-pyroglutamic acid: penmacric acid and analogues

Alkylation reactions using alpha-halolactams or lactam enolates derived from bicyclic lactam templates can proceed with high endo- or exo- diastereoselectivity respectively. In the latter case, stereochemical correction by means of enolate generation and hindered phenol quench is possible with moderate efficiency. This protocol has been applied to the synthesis of protected penmacric acid and its analogues.     

Manganese Dioxide Mediated Stereoselective, One-step Synthesis of Novel Steroidal (6R)-Spiro-1’,2’,4’-triazoline-3’-thiones

Oxidative cyclization of 5α-cholestan-6-one thiosemicarbazone (1), its 3β-chloro (2) and 3β-acetoxy (3) analogues with active manganese dioxide at room temperature afforded selectively the corresponding (6R)-spiro-1’,2’,4’-triazoline-3’-thiones 4—6. This synthesis has the advantages of mild reaction conditions, easy handling, easily available reagent and high yields. The products have been characterized by analytical and spectral data.