Swarna Gamage - Academia.edu (original) (raw)
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![Research paper thumbnail of Comparative biodistribution and metabolism of carbon-11-labeled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide and DNA-intercalating analogues](https://attachments.academia-assets.com/119949184/thumbnails/1.jpg)
](Cancer research, 2001
The tricyclic carboxamide N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is a DNA-interc... more The tricyclic carboxamide N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is a DNA-intercalating agent capable of inhibiting both topoisomerases I and II and is currently in Phase II clinical trial. Many related analogues have been developed, but despite their potent in vitro cytotoxicities, they exhibit poor extravascular distribution. As part of an ongoing drug development program to obtain related "minimal intercalators" with lower DNA association constants, we have compared the biodistribution and metabolite profiles of the prototype compound, DACA, with three analogues to aid rational drug selection. All of these compounds share a common structural feature, N-dimethyl side chain, which was radiolabeled with the positron-emitting radioisotope, carbon-11. This strategy was selected because it allows promising candidates emerging from preclinical studies in animals to be evaluated rapidly in humans using positron emission tomography (PET). The acridine DACA, the ...
A new synthesis of substituted acridine-4-carboxylic acids and the anticancer drug N-[2-(dimethylamino) ethyl] acridine-4-carboxamide (DACA)
Tetrahedron letters, 1997
... fights resexved 00404039 97 17.00 + 0.00 A New Synthesis of Substituted Aeridine4carboxylic A... more ... fights resexved 00404039 97 17.00 + 0.00 A New Synthesis of Substituted Aeridine4carboxylic Acids and the Anticancer Drug N [2(Dimethylamino)ethyl] acridine4carboxamide (DACA) Swarna A. Gamage ... Sharma, R.; Voynov, GH; Ovaska, T .V.; Marquez, VE Synlett 1995, 839. ...
Synthesis and biological evaluation of novel acylphloroglucinols
Anesthesia and analgesia, Jan 27, 2015
Ketamine is a well-established, rapidly acting dissociative anesthetic. Clinical use is limited b... more Ketamine is a well-established, rapidly acting dissociative anesthetic. Clinical use is limited by prolonged psychotomimetic phenomena on emergence, often requiring the coadministration of additional hypnotic drugs. We hypothesized that the development of ketamine ester analogs with ultrashort offset times might markedly reduce the dysphoric emergence phenomena and, hence, increase the utility of a ketamine-like hypnotic and analgesic. Here, we describe the results of studies that seek to define the pharmacology of 5 esters of ((1-(2-chlorophenyl)-2-oxocyclohexyl)amino)pentanoate hydrochloride, the first ketamine analogs designed to be susceptible to ultrarapid metabolism. Five norketamine ester analogs (R1-R5) were compared by ability to produce loss of righting and nociceptive blunting in rats. Toxicity testing was performed for 2 analogs (R1, R5) with 50% lethal dose (LD50) estimation in rats. In vitro metabolic stability was tested in rabbit plasma and whole blood by high-perfor...
Cancer research, 2001
The tricyclic carboxamide N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is a DNA-interc... more The tricyclic carboxamide N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is a DNA-intercalating agent capable of inhibiting both topoisomerases I and II and is currently in Phase II clinical trial. Many related analogues have been developed, but despite their potent in vitro cytotoxicities, they exhibit poor extravascular distribution. As part of an ongoing drug development program to obtain related "minimal intercalators" with lower DNA association constants, we have compared the biodistribution and metabolite profiles of the prototype compound, DACA, with three analogues to aid rational drug selection. All of these compounds share a common structural feature, N-dimethyl side chain, which was radiolabeled with the positron-emitting radioisotope, carbon-11. This strategy was selected because it allows promising candidates emerging from preclinical studies in animals to be evaluated rapidly in humans using positron emission tomography (PET). The acridine DACA, the ...
A new synthesis of substituted acridine-4-carboxylic acids and the anticancer drug N-[2-(dimethylamino) ethyl] acridine-4-carboxamide (DACA)
Tetrahedron letters, 1997
... fights resexved 00404039 97 17.00 + 0.00 A New Synthesis of Substituted Aeridine4carboxylic A... more ... fights resexved 00404039 97 17.00 + 0.00 A New Synthesis of Substituted Aeridine4carboxylic Acids and the Anticancer Drug N [2(Dimethylamino)ethyl] acridine4carboxamide (DACA) Swarna A. Gamage ... Sharma, R.; Voynov, GH; Ovaska, T .V.; Marquez, VE Synlett 1995, 839. ...
Synthesis and biological evaluation of novel acylphloroglucinols
Anesthesia and analgesia, Jan 27, 2015
Ketamine is a well-established, rapidly acting dissociative anesthetic. Clinical use is limited b... more Ketamine is a well-established, rapidly acting dissociative anesthetic. Clinical use is limited by prolonged psychotomimetic phenomena on emergence, often requiring the coadministration of additional hypnotic drugs. We hypothesized that the development of ketamine ester analogs with ultrashort offset times might markedly reduce the dysphoric emergence phenomena and, hence, increase the utility of a ketamine-like hypnotic and analgesic. Here, we describe the results of studies that seek to define the pharmacology of 5 esters of ((1-(2-chlorophenyl)-2-oxocyclohexyl)amino)pentanoate hydrochloride, the first ketamine analogs designed to be susceptible to ultrarapid metabolism. Five norketamine ester analogs (R1-R5) were compared by ability to produce loss of righting and nociceptive blunting in rats. Toxicity testing was performed for 2 analogs (R1, R5) with 50% lethal dose (LD50) estimation in rats. In vitro metabolic stability was tested in rabbit plasma and whole blood by high-perfor...