Pyrimidine-5-carbonitriles II: synthesis and antimicrobial activity of novel 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles.

New series of 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 6-alkyl-2-thiouracil-5-carbonitriles 4c,d, 6-alkyl-2-arylmethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 5a-p, 6-alkyl-2-(2-methoxyethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 6a-d, 6-alkyl-2-benzyloxymethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 7a-c, 6-alkyl-2-(5-nitrofuran-2-ylmethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 8a-d, 6-alkyl-4-arylthio-2-(benzylsulfanyl)pyrimidine-5-carbonitriles 10a, b and 2-benzylsulfanyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-6-pentylpyrimidine-5-carbonitrile 11, were synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 4d, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5 l, 5p, 7a, 7b, 7c, 8a, 8b, 8c, 8d and 11 -displayed marked antibacterial activity particularly against the tested Gram-positive bacteria. Meanwhile, none of these compounds were proved to be active against Candida albicans.

Chemotherapy management of malignant pleural mesothelioma: a phase II study comparing two popular chemotherapy regimens.

PURPOSE: The aim of this prospective, phase II clinical study is to evaluate the activity of gemcitabine and cisplatin in comparison to pemetrexed and carboplatin in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: The patients were recruited from May 2008 to May 2011. One group included 21 cases who received cisplatin and gemcitabine. The other group included 19 cases who received pemetrexed and carboplatin. RESULTS: Response is superior in the pemetrexed group (p = 0.041). The median follow-up was 18 months (range 6-30 months). Cumulative survival at 1.5 years was 57.8 % for the pemetrexed carboplatin group. For the gemcitabine cisplatin group, the cumulative survival proportion at 1.5 years was 41 % (p = 0.0599). CONCLUSIONS: Pemetrexed plus carboplatin are a step forward in the treatment of mesothelioma, the prognosis for these patients remains poor. Cheaper combinations as gemcitabine and cisplatin may be considered sufficient to treat cases with advanced mesothelioma.

Medulloblastoma: conventional radiation therapy in comparison to chemo radiation therapy in the post-operative treatment of high-risk patients.

UNLABELLED: The aim of this study is to assess treatment results of 48 pediatric high-risk medulloblastoma cases that were treated by surgery, radiotherapy with or without chemotherapy. The impact of adjuvant combination chemotherapy on treatment results will be assessed. Forty-eight cases of pediatric high-risk medulloblastoma treated from July 2001 to July 2004 were randomized into two groups. The first (group I) included 21 patients who received postoperative craniospinal radiation therapy (36Gy+boost 20Gy to the posterior fossa). The second (group II) included 27 cases who received postoperative combination cranio-spinal radiation therapy (with the same dose as the first group) and chemotherapy (vincristine, etoposide, cisplatin). Both groups were compared as regards overall survival (OS), disease free survival (DFS), response rate and treatment toxicity. In-group I, complete remission (CR) was achieved in 71.4% of the cases; partial remission (PR) in 14.3% of the patients; stationary disease (SD) in 14.3% and none of the cases suffered from progressive disease. The three-year OS was 69.5% and the three-year DFS was 61.3%. In-group II, CR was achieved in 59.3% of the cases; PR in 3.7%; SD in 3.7% and PD in 37.3% of the cases. The three-year OS was 48.4% and the 3-year DFS was 48.9%. Regarding acute treatment toxicity in group I, nine patients (31.5%) developed grade I myelo-suppression and seven cases (24.5%) developed grade II myelo-suppression with three to five days treatment interruption. Whereas in group II, 13 patients (45.5%) developed grade I myelosuppression and seven cases (24.5%) developed grade II myelo-suppression requiring interruption of treatment for a period ranging from five to seven days with spontaneous recovery. In group I no other acute toxicity was recognized, whereas in group II other toxicities related to chemotherapy were noticed. For example, three patients (11%) developed peripheral neuritis during the course of treatment and two patients (7%) developed renal impairment, which responded to medical treatment. Late treatment toxicity, manifested as reduction in intelligence quotient (IQ), was noticed, which makes conventional treatment of medulloblastoma unsatisfactory. In group I; 13 patients (62%) suffered a reduction of 8-20% in IQ in comparison to their normal siblings, whereas in Group II; 13 patients (48%) developed a reduction in IQ ranging from 12-21%. CONCLUSION: The current treatment of medulloblasotma has a detrimental effect on long-term survivors. Whereas acute toxicity is considered mild and tolerable, late toxicity regarding diminution in IQ makes current treatment unsatisfactory because of the long-term mental disability of the cured patients. We believe that, the poorer outcome in the chemo-radiation group was due to the treatment interruption during radiation therapy caused by myelosuppression since the incidence of myelosuppression was higher in the chemo-radiation group and the recovery time was longer.

Fattiviracin A1, a novel antiherpetic agent produced by Streptomyces microflavus Strain No. 2445. I. Taxonomy, fermentation, isolation, physico-chemical properties and structure elucidation.

A novel antiherpetic agent, fattiviracin A1, was isolated from the culture broth of strain No. 2445 identified as Streptomyces microflavus. It was purified through 1-butanol extraction, column chromatographies on Diaion HP-10 and silica gel and HPLC using a reverse phase column. The structure of fattiviracin A1 was determined by several spectroscopic experiments and chemical degradations. It is a new macrocyclic diester consisting of four D-glucose units and two (C24 and C33) hydroxy fatty acids. It is closely related to cycloviracins B1 and B2, but differs from these known compounds in both the length of its side chain and the sugar moiety.

An apparatus for the precise determination of lifetimes of atomic states.

The time which elapses between excitation of an atom by a pulse of light and subsequent emission of radiation may be measured by a delayed coincidence technique. A system which is suitable for measuring lifetimes of atomic states in the range 10(-7)-10(-8) sec, employing a high speed Kerr shutter in conjunction with a time-to-pulse height converter and kicksorter, is described.