R K Zee-Cheng — Page 2

PubMed1976

Tetramethoxydibenzoquinolizinium salts. Preparation and antileukemic activity of some positional and structural isomers of coralyne.

Some positional and structural isomers of coralyne were prepared and evaluated in the P388 lymphocytic leukemia system for their inhibitory activity. The levels of antileukemic activity of coralyne, neocoralyne, isocoralyne, and stracoralyne were comparable, thus implying that two sets of the N-O-O triangular pharmacophore in a condensed isoquinoline molecule are preferable and the angle between these two sets has little influence on antileukemic activity. The importance of the environment around the C5-C6 region of the dibenzo[a,g]quinolizine ring to antileukemic activity was demonstrated by the activity differences between coralyne and allocoralyne.

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PubMed1975

Preparation and antileukemic activity of some alkoxybenzo(c)phenanthridinium salts and corresponding dihydro derivatives.

Salts of 2,3,8,9-tetrasubstituted alkoxy-, hydroxy-, and acetoxybenzo(c)phenanthridines as well as the corresponding 6-methoxy-5,6-dihydrobenzo(c)phenanthridines were prepared from appropriate chalcones through the tetralone and the 4b,10b,11,12-tetrahydrobenzo(c)phenanthridine intermediates. Complete O-demethylation of the tetramethoxybenzophenanthridine was achieved by fusion with pyridine hydrochloride at elevated temperature. The title compounds are active against leukemias L1210 and P388 in mice and some are curative against Lewis lung carcinoma. The importance of the nature of the environment about the nitrogen atom of these compounds and the substituents is discussed. 3,4-Dimethoxy-3,4-methylenedioxychalcone possesses activity against leukemia P388.

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PubMedDate not supplied

Delivery of anticancer drugs.

Chemotherapy is a major therapeutic approach for the treatment of both localized and metastasized cancers. Since anticancer drugs are neither specific nor targeted to the cancer cells, improved delivery of anticancer drugs to tumor tissues in humans appears to be a reasonable and achievable challenge. Scientists are working to increase the availability of drug for tumor uptake by 1) delaying the release preparations for long-lasting actions; 2) using liposome-entrapped drugs for prolonged effect or reduced toxicity; 3) administrating inert, non-toxic prodrugs for specific activation at the tumor site; 4) delivering the antibody-mediated drugs; or 5) conjugating site-specific carriers to direct the drug to the tumor target. The latter depends heavily on pharmacokinetic investigations. Some success has been achieved in enhancing the efficacy and reducing the toxicity of drugs. Pharmacokinetic and pharmacodynamic considerations are two areas which have been focused toward the quantitative pharmacological studies of anticancer drugs in this manuscript. This review covers biodistribution and elimination, furnishing information on body clearance and unveiling sites of major metabolism; administration of anticancer drugs via various routes for optimal utilization; intra-arterial infusion for localized tumors, intrathecal, intraperitoneal and intrapleural injection for regional cavity administration. Conventional delivery routes, doses, pharmacokinetics data and elimination routes of therapeutic anticancer drugs are tabled. General approaches for delivery of anticancer drugs in achieving therapeutic improvements are outlined and correlated. Mechanism of drug resistance, and specific changes affecting the delivery of available chemotherapeutic agents, as well as the drugs to restore the sensitivities to agents of resistant tumor cells, are discussed. This monograph covers the developments and progress in the delivery of anticancer drugs in two approaches: the theoretical approach, including pharmacokinetic and pharmacodynamic considerations, therapeutic implications and mechanism of drug resistance, and the practical approach, including the physical, chemical, biochemical and physiological considerations. Among these, the physical approach for the delivery of anticancer agents to target sites (via microparticulate drug carriers: nanoparticles, liposomes, microspheres and activated carbon as well as the magnetic microcapsules) has shown recognizable improvements in prolonging anticancer effects and reducing toxicities. Implantable pumps and reservoirs for regional chemotherapy provide external control of delivery rate. The implanted systems, in general, yield better results than the traditional treatments in the treatment of liver and brain cancer. Chemical approaches for the improvement of drug delivery use prodrugs, biodegradable polymers and macromolecular matrix techniques.(ABSTRACT TRUNCATED AT 400 WORDS)

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