RESUMEN

We developed a concise protocol for the synthesis of ellipticine quinone from the appropriate 3-iodoindole-2-carbaldehydes in four steps. The key step is the construction of carbazole-1,4-quinone through tandem Ring-Closing Metathesis (RCM) and dehydrogenation under oxygen atmosphere. Therefore, the ellipticine quinone analogs possessing substitution at the 8- and/or 9-positions were synthesized using this method. In total, 14 compounds were evaluated for antiproliferative activity against HCT-116 and HL-60 cell lines; 9-nitroellipticine quinone was found to have superior activity compared to calothrixin B.

Asunto(s)

Antineoplásicos/farmacología , Benzoquinonas/farmacología , Elipticinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzoquinonas/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Elipticinas/química , Humanos , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales Cultivadas

RESUMEN

Large-scale (180 × 60 × 1 mm(3)) transmission gratings with groove densities of 1250 and 1740 lines/mm have been developed, resulting in diffraction efficiencies above 95%. The throughput of a folded pulse compressor with two large-scale transmission gratings was approximately 80% in a 20-fs Ti:sapphire chirped-pulse amplification (CPA) laser. The parabolic bending of the transmission grating due to anti-reflection (AR) coating was minimized to 2.9 λ at 633 nm by improving the evaporation process. By a simple analysis, we explain why this level of bending does not induce a wavefront distortion through the transmission grating near the Littrow condition while the wavefront from a reflection grating is distorted to nearly twice the bending of the grating. The calculation based on the measured bending shows that both the group delay difference relative to the ideally flat grating from 750 to 850 nm and the spatial pulse front distortion over a 60-mm-diameter input beam are negligible, even when the dispersive beam covers ~140 mm on the grating. The spatial pulse front distortion measured after the compressor was less than the measurement limit (1.5 fs) for a 20-mm-diameter beam, where the beam size in the dispersive direction on the grating was 85 mm.

RESUMEN

Methyl methanesulphonate (MMS), a potent alkylating agent and testicular toxicant, was orally administered to rats for 5 days at 40 mg/kg. During the recovery period of up to 5 weeks, males were evaluated for testicular toxicity and sperm morphology. The 5-week recovery period were designated as follows: Day 1 (the day after final treatment); Week 1, Week 2, Week 3, Week 4 and Week 5 (1, 2, 3, 4 and 5 weeks after final treatment). Morphologically abnormal sperm increased beginning in Week 3, peaked in Week 4 and declined slightly in Week 5. Histopathological examinations indicated retention of step 19 spermatids at stage IX from Day 1 through Week 3. Quantitative evaluation of spermatogenic cells indicated a decrease in the number of late pachytene spermatocytes and early spermatids on Day 1. TUNEL examination showed a significantly high frequency of apoptosis in the meiosis cells in Week 1. In the present study, genetic damage induced by treatment with MMS affected spermatogenesis and a wide variety of spermatogenic cells in the testis. Apoptosis in the course of meiosis seemed to be involved in the elimination process of genetically insulted germ cells, and this process seems to play an important role in eliminating and/or decreasing the germ cells with retention of spermatids and the potential to express morphologically abnormal spermatozoa.

Asunto(s)

Metilmetanosulfonato/toxicidad , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Epidídimo/metabolismo , Epidídimo/patología , Histocitoquímica , Etiquetado Corte-Fin in Situ , Masculino , Tamaño de los Órganos/efectos de los fármacos , Tamaño de los Órganos/fisiología , Ratas , Ratas Sprague-Dawley , Organismos Libres de Patógenos Específicos , Recuento de Espermatozoides , Cabeza del Espermatozoide/patología , Espermatozoides/patología , Testículo/metabolismo , Testículo/patología

RESUMEN

Isoquinoline derivatives were synthesized from cyclobutenylmethylamine derivatives having an alkyne moiety in a tether using a second-generation ruthenium carbene complex under ethylene gas in good yields.

RESUMEN

[formula: see text] ROM-RCM (ring-opening and ring-closing metatheses) of cycloalkene-yne was demonstrated using a second-generation ruthenium complex. When cycloalkene bearing the alkyne moiety at the C-1 position was reacted with a ruthenium-carbene complex under an atmosphere of ethylene, ROM-RCM proceeded smoothly to give bicyclic compound and/or dimeric compound in good yields.