ABSTRACT
A novel series of the biheterocycles-based compounds with core structure distinguished from combretastatin A-4 (1) and colchicine (5) have been synthesized and evaluated as potent anti-mitotic agents. Compound 1-(4'-Indolyl and 6'-quinolinyl)-4,5,6-trimethoxyindoles 13 and 19 showed substantial anti-proliferative activity against various human cancer cell lines, regardless to the tissue origin and the expression of multiple-drug resistance MDR1, with a mean IC(50) value of 38 and 24 nM respectively. Compound 13 (IC(50) = 1.7 µM) also exhibited similar anti-tubulin activities to 1 (IC(50) = 1.8 µM) and displayed strong binding property to the colchicine binding site on the microtubules. Computational modeling analysis revealed that the binding mechanism of compound 13 is similar to that of CA4.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Indoles/chemical synthesis , Indoles/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Indoles/chemistry , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Models, Molecular , Spectrometry, Mass, Electrospray Ionization , Tubulin/metabolismABSTRACT
This article studied differences in postpartum fatigue and birth outcomes between women who pushed immediately and those who delayed pushing during the second stage of labor. Data were collected from primiparous women in their 38th to 42nd gestational week who did not receive epidural analgesia during labor and were free of complications during pregnancy. Using a quasi-experimental design, 72 participants selected by convenient sampling were assigned based on individual participant's preference to either an experimental or control group. For the experimental group, pushing was delayed until the point after full cervical dilation at which (a) the mother felt a strong physical pushing reflex, (b) the fetal head had both descended to at least the +1 level in the pelvis and turned to the occiput anterior position, and (c) uterine contractions were at least 30 mmHg. For the control group, the physician instructed mothers to begin pushing after full cervical dilation at the point when the fetal head was in the occiput anterior position and uterine contractions were at least 30 mmHg. The authors administered the Modified Fatigue Symptom Checklist at 1 and 24 hr after delivery to measure participant's fatigue levels. Birth outcomes were assessed based on medical chart data. Findings showed a significant difference between the two groups in terms of 1- and 24-hr postpartum fatigue scores. The duration of the second labor stage (experimental group, 70.31 +/- 37.17 min; control group, 129.06 +/- 75.69 min) also differed significantly. The group that pushed immediately recorded higher cesarean and instrument-assisted birth rates. No significant differences were observed in terms of perineal tears, maternal/neonatal complications, or neonatal Apgar scores. Results of this study provide important insights for caregivers working in the delivery room and suggest that current care procedures change to include the delayed pushing during the second stage of labor. By delaying pushing exertions until the mother feels a reflexive urge to do so, mothers' feelings of fatigue are significantly reduced.
