Synthesis, Anti-Inflammatory, and Ulcerogenicity Studies of Novel Substituted and Fused Pyrazolo[3,4-d]pyrimidin-4-Ones.

Synthesis, Anti-Inflammatory, and Ulcerogenicity Studies of Novel Substituted and Fused Pyrazolo[3,4-d]pyrimidin-4-ones.

Sci Pharm. 2013 Jun; 81(2): 393-422
El-Tombary AA

In the present investigation, some new pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives (7-12) as well as fused pyrazolo[3′,4′:4,5]pyrimido[1,2-b]pyridazin-4(1H)-one (14-16) and 7,8,9,10-tetrahydropyrazolo[3′,4′:4,5]pyrimido[1,2-b]-cinnolin-4(1H)-one (17) ring systems were synthesized using the starting compound 5-amino-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (5). The structures of the newly synthesized compounds were elucidated by IR, (1)H NMR, (13)C NMR, mass spectroscopy, and elemental analysis. The theoretical calculation of their lipophilicity as C log P was performed. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw edema test in rats using indomethacin as the reference drug. Ulcer indices for the most active compounds were calculated. Seven compounds (10b, 11a-f) showed consistently good anti-inflammatory activity. In particular, 5-{[4-(4-bromophenyl)-3-(4-chlorophenyl)-1,3-thiazol-2(3H)-ylidene]amino}-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (11e) and its 3,4-bis(4-chlorophenyl) analog (11f) were found to be the most effective among the other derivatives, showing activity comparable to that of indomethacin with minimal ulcerogenic effects. Correlation of the biological data of the active compounds with their theoretically calculated C log P values revealed that lipophilicity influences the biological response. HubMed – drug


7-Aza-des-A-steroids with Antimicrobial and Cytotoxic Activity.

Sci Pharm. 2013 Jun; 81(2): 329-38
Krojer M, Keller M, Bracher F

This paper describes a convenient approach to the 7-aza-des-A-steroid (6,6a,7,8,9,9a-hexahydro-5H-cyclopenta[h]quinoline) scaffold starting from Grundmann’s ketone using two different pyridine annulation protocols. The biological evaluation of the pyridine and pyridinium products revealed that these compounds unexpectedly do not interfere with ergosterol and cholesterol biosynthesis. The pyridinium compound 6 showed significant antimicrobial and cytotoxic activities which are most likely due to its detergent-like structure. HubMed – drug


Novel Phenotypic Fluorescent Three-Dimensional Platforms for High-throughput Drug Screening and Personalized Chemotherapy.

J Cancer. 2013; 4(5): 402-15
Fang C, Avis I, Salomon D, Cuttitta F

We have developed novel phenotypic fluorescent three-dimensional co-culture platforms that efficiently and economically screen anti-angiogenic/anti-metastatic drugs on a high-throughput scale. Individual cell populations can be identified and isolated for protein/gene expression profiling studies and cellular movement/interactions can be tracked by time-lapse cinematography. More importantly, these platforms closely parallel the in vivo angiogenic and metastatic outcomes of a given tumor xenograft in the nude mouse model but, unlike in vivo models, our co-culture platforms produce comparable results in five to nine days. Potentially, by incorporating cancer patient biopsies, the co-culture platforms should greatly improve the effectiveness and efficiency of personalized chemotherapy. HubMed – drug


Pericardial synovial sarcoma in a dyspnoeic female with tuberculous pericarditis: A case report.

Oncol Lett. 2013 Jun; 5(6): 1973-1975
Wu X, Chen R, Zhao B

Synovial sarcomas of the pericardium are extremely rare and associated with poor survival rate. The current case report describes a 45-year-old female who presented with dyspnea upon exertion, a paroxysmal cough, night sweats and recurrent pericardial effusion. The patient was diagnosed with tuberculous pericarditis and received antituberculous drug therapy. Echocardiography and magnetic resonance imaging (MRI) revealed a pericardial mass lying predominantly over the right atrium. The patient was treated by surgical excision and a subsequent histological analysis confirmed the diagnosis of a pericardial synovial sarcoma. Under high power examination, a characteristic biphasic appearance consisting of hypercellular spindled cell sheets was observed. Immunohistochemistry demonstrated positive staining for epithelial membrane antigen (EMA), vimentin and Bcl 2. The patient was then referred for adjuvant chemotherapy with a combination of adriamycin and ifosfamide. The patient has since remained clinically free of disease for 32 months. HubMed – drug