A series of substituted 2-arylnaphthyridin-4-one analogues, which were previously synthesized in our laboratory, were evaluated for their in vitro cytotoxic activity against human lung cancer A549 and human renal cancer Caki-2 cells using MTT assay. Some compounds (11, 12, and 13) showed stronger cytotoxicity than colchicine against both tumor cell lines, and compound 13 exhibited the most potent activity with IC50 values of 2.3 and 13.4 micrometer, respectively. Three-dimensional quantitative structure activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed. Predictive 3D-QSAR models were obtained with q(2) values of 0.869 and 0.872 and r(2)(ncv) values of 0.983 and 0.993 for CoMFA and CoMSIA, respectively. These results demonstrate that CoMFA and CoMSIA models could be reliably used in the design of novel cytotoxic agents.
Cell Line, Tumor ; Colchicine ; Cytotoxins ; Humans ; Inhibitory Concentration 50 ; Kidney Neoplasms ; Lung Neoplasms ; Quantitative Structure-Activity Relationship

Naphthyridine compounds are important, because they exhibit various biological activities including anticancer, antimicrobial, and anti-inflammatory activity. Some naphthyridines have antimitotic effects or demonstrate anticancer activity by inhibiting topoisomerase II. These compounds have been investigated as potential anticancer agents, and several compounds are now part of clinical trials. A series of naphthyridine derivatives were evaluated for their in vitro cytotoxic activities against human cervical cancer (HeLa), leukemia (HL-60), and prostate cancer (PC-3) cell lines using an MTT assay. Some compounds (14, 15, and 16) were more potent than colchicine against all three human cancer cell lines and compound (16) demonstrated potency with IC50 values of 0.7, 0.1, and 5.1 microM, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used for quantitative structure-activity relationship (QSAR) molecular modeling of these compounds. We obtained accurate and predictive three-dimensional QSAR (3D-QSAR) models as indicated by the high PLS parameters of the HeLa (q2, 0.857; r2, 0.984; r2pred, 0.966), HL-60 (q2, 0.777; r2, 0.937; r2pred, 0.913), and PC-3 (q2, 0.702; r2, 0.983; r2pred, 0.974) cell lines. The 3D-QSAR contour maps suggested that the C-1 NH and C-4 carbonyl group of the naphthyridine ring and the C-2 naphthyl ring were important for cytotoxicity in all three human cancer cell lines.
Antineoplastic Agents ; Cell Line ; Colchicine ; DNA Topoisomerases, Type II ; Humans* ; Inhibitory Concentration 50 ; Leukemia* ; Models, Molecular ; Naphthyridines ; Prostate* ; Prostatic Neoplasms* ; Quantitative Structure-Activity Relationship ; Structure-Activity Relationship* ; Uterine Cervical Neoplasms*

BACKGROUND: Hypotension is one of the most common complications from the spinal anesthesia frequently used for surgery on the lower abdomen or extremities. It might be important in prognostic improvements to maintain cardiovascular homeostasis in elderly or patients with cardiovascular diseases. This study evaluated the effect of the patients' position on the preservation of cardiovascular stability when elderly patients suffering from hypertension undergo surgery for an axillo-femoral arterial bypass. METHODS: 24 patients with hypertension undergoing an elective axillo-femoral bypass surgery were examined. The patients were randomly allocated into two groups (Lateral 20 min group: patients with lateral position for 20 min after spinal anesthesia; Supine group: patients with the supine position immediately after spinal anesthesia). The observers recorded the hemodynamic variables, as well as the loss of sensation on both sides. RESULTS: Considering the changes in the arterial blood pressure and heart rate from the baseline values, patients in the supine group showed a greater decrease in arterial blood pressure and heart rate (P < 0.05). In the lateral 20 min group, there was a lower block level of cold sensation that reflected the sympathetic blockade at the non-operated site (P < 0.05). CONCLUSIONS: The lateral decubitus position for 20 min after spinal anesthesia can contribute to the maintenance of cardiovascular stability during unilateral axillo-femoral bypass surgery in elderly patients with hypertension.
Abdomen ; Aged ; Anesthesia, Spinal* ; Arterial Pressure ; Blood Pressure* ; Cardiovascular Diseases ; Extremities ; Heart Rate* ; Heart* ; Hemodynamics ; Homeostasis ; Humans ; Hypertension ; Hypotension ; Sensation ; Supine Position