Synthesis and antitumor activity of camptothecin- 4β-triazolopodophyllotoxin conjugates

Abstract

Two new compounds (9 and 10) having a camptothecin (CPT) analog conjugated to the 4β-azido-4-deoxypodophyllotixin analog by untilizing the copper-catalyzed azide-alkyne cycloadditon (CuAAC) reaction, and were evaluated for their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using the MTT (3-(4,5-dimethyl-thiahiazo-2-yl)-2,5-diphenyltetrazolium bromide) assay. Two novel conjugates shown weak cytotoxicity, compound 10 showed highly potent against HL-60 cell line tested, with IC₅₀ value 17.69?±?0.19?μM. This compound suggested its potential as anticancer agents for further development.

     

Peptide late-stage C(sp3)–H arylation by native asparagine assistance without exogenous directing groups

There is a strong demand for novel native peptide motifs for post-synthetic modifications of peptides without pre-installation and subsequent removal of directing groups. Herein, we report an efficient method for peptide late-stage C(sp³)–H arylations assisted by the unmodified side chain of asparagine (Asn) without any exogenous directing group. Thereby, site-selective arylations of C(sp³)–H bonds at the N-terminus of di-, tri-, and tetrapeptides have been achieved. Likewise, we have constructed a key building block for accessing agouti-related protein (AGRP) active loop analogues in a concise manner.

An efficient method for peptide late-stage C(sp³)-H arylations assisted by unmodified side chain of asparagine (Asn) without any exogenous directing group has been reported.     

One-pot two-step microwave-assisted reaction in constructing 4,5-disubstituted pyrazolopyrimidines

[reaction: see text] A microwave-assisted reaction was developed to facilitate the construction of 4,5-disubstituted pyrazolopyrimidines. This one-pot two-step process involves a sequential S(N)Ar displacement of the C4 chloro substituent with various anilines and amines, followed by a Suzuki coupling reaction with different boronic acids. Using microwave irradiation leads to high product conversion, low side product formation, and shorter reactions.     

Microdialysis sampling coupled to HPLC for transdermal delivery study of ondansetron hydrochloride in rats

The transdermal delivery of ondansetron hydrochloride (ON) solution in propylene glycol (PG) with a widely used penetration enhancer, oleic acid (OA), was studied in rats by a microdialysis sampling technique. Dialysate samples collected from the probe were directly injected into the HPLC system without any pre-treatment and no interference occurred in the blank sample. A good linearity between the standard concentrations and peak areas within the calibration range was achieved. In vivo recovery (32.52 +/- 1.8%) of the probe was assessed with the retrodialysis method, which was used to calculate the ON concentration in the dermis. Oleic acid at the concentrations of 2% and 5% (w/v) increased the steady-state delivery rate from 0.001 to 0.030 and 0.058 microg/h, respectively. OA proved to be an effective enhancer for transdermal delivery of ON in rats.     

Characterizing the dynamics of auditory perception

After listening to a sound that is presented repeatedly, subjects report hearing different transforms of the original sound. The frequency of reported transforms is a sensitive index of some speech disorders as well as cognitive flexibility in aging. In this paper, we propose and investigate quantitative measures that characterize the dynamics of this phenomenon, known as the verbal transformation effect. In particular, we show that the distribution of the dwell time, the time spent perceiving a string of a given phonemic form before switching to another form, obeys a power law for normal subjects with an exponent valued between 1 and 2. This result suggests that within this paradigm there is no characteristic time scale for the perceptual process. Additionally, we analyze the correlation properties of the transforms. We suggest that the complexity measures and techniques introduced here might be useful diagnostic tools for a number of speech and cognitive disorders. (c) 1995 American Institute of Physics.     

The projection method for computing multidimensional absolutely continuous invariant measures

We present an algorithm for numerically computing an absolutely continuous invariant measure associated with a piecewiseC ² expanding mappingS: on a bounded region R ^N. The method is based on the Galerkin projection principle for solving an operator equation in a Banach space. With the help of the modern notion of functions of bounded variation in multidimension, we prove the convergence of the algorithm.