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Success of glaucoma filtration surgery is influenced by the wound healing response. Attention has been focused on pharmacological agents to control a process that leads to excessive scarring and eventual failure of glaucoma filtration surgery. Several agents, including 5-fluorouracil and mitomycin C, as well as other antiproliferative drugs will be discussed. Newer antifibrotic agents and novel drug delivery systems are under development in tissue culture and animal models in an effort to improve efficacy and safety. This article summarizes current treatment modalities and future prospects to prevent excessive wound healing and improve the success of glaucoma filtration surgery.

Indolo[3,2-b]quinoline derivatives (1b-i) with a methyl group at each possible position have been synthesized. The 1-methyl (1b) and 9-methyl (1i) derivatives were inactive, but the 3-methyl (1d), 4-methyl (1e), and 6-methyl (1f) derivatives exhibited high treatment/control (T/C) value and cure rates against leukemia P388 in mice. These results indicated that modification of indolo[3,2-b]quinoline derivatives at 3, 4, and 6 positions may be useful approach for lead optimization.

Introduction: In the Americas, Lutzomyia longipalpis has been incriminated as the vector of visceral leishmaniasis in almost all the areas in which this disease has been reported. The notification of human cases of visceral leishmaniasis and the presence of dogs with an appearance suggestive of the disease in the country of Corumbá, Mato Grosso do Sul State, Brazil, led us to undertake an entomological investigation in this area, for the purpose of identifying the phlebotomine vector., Material and Method: The county of Corumbá is located in the Pantanal region and its urban area is situated at 18 degrees 59' 44" South and 57 degrees 39' 16" West. The research project was carried out in peri and intradomiciliary environments, in three urban districts, one of which was central and the other two on the outskirts, and in a cave situated outside the urban perimeter. Most of the captures were made weekly with light automatic traps, in the period from February 1984 to December 1986. Meteorological data for this period were obtained from the city's meteorological station and those for the period from 1925 to 1982 from the literature., Results: The urban phlebotomine fauna consisted of eight species and was similar to that of the cave, except that in the latter the species were more abundant. Lutzomyia cruzi was predominant in the peri and intradomiciliary environments. Its prevalence in the central district was of 90.3% and lower in the outskirts. Lu. forattinii presented considerable prevalence (39.0%) in one of the outlying districts too. In the cave, Lu. corumbaensis was the predominant species, followed by Lu. sordellii, Lu. forattinii, Lu. peresi and Lu. cruzi. The impact of the climatic condition and the action of insecticides in the urban area on the frequency of the species, as well as the use of the cave as a breeding ground by the phlebotomines, in view of the changes in the sex rate, are commented. Data on anthropophily and captures of Lu. forattinii using dog bait have been added., Conclusion: The predominance of Lu. cruzi in the urban area; the great prevalence of Lu. forattinii in most of the outlying areas studied and the anthropophily of this latter species, as well as the strong affinity of these species with Lu. longipalpis, the main vector of visceral leishmaniais in other areas of the Americas, suggest the participation of both in the transmission of the disease in Corumbá.

Indolo[3,2-b]quinoline derivatives (1) having various amine moieties were prepared and their antitumor activities against P388 leukemia in mice were evaluated, for the purpose of gaining an insight into the role of the amine moiety in the antitumor activity and searching for an effective amine moiety. Introduction of a methylene group between the phenyl group and amino or methanesulfonamido group resulted in decrease or loss of activity.

We have used a 5' fragment of the gene GTF2D, which encodes human transcription factor IID, and Chinese hamster-mouse somatic cell hybrids to map the murine homologue, Gtf2d, to a single locus on mouse chromosome 17 (Chr 17). Linkage analysis of progeny from an interspecific backcross localized the gene near the marker D17Leh66 in the proximal region of Chr 17.

Novel indolo[3,2-b]quinolines (1b-k), having a nitro, amino, acetamido, methanesulfonamido, or glycosylamino group at the 2, 7, or 8-position, were prepared and their antitumor activities against P388 leukemia in mice were examined. The 7-galactopyranosylamino derivative (1g) showed the most potent activity (optimal dose = 25 mg/kg, T/C greater than 333%, cure rate 5/6).

Novel indolo[3,2-b]quinoline derivatives (1c--f), which carried a methoxy or a hydroxy group at the 4- or 7-position of the lead compound 1a, were prepared and their antitumor activities against P388 in mice were examined. Except for the 4-hydroxy derivative (1d), these showed remarkably potent activity. Among these compounds, the 7-hydroxy derivative (1f) was the most potent one (optimal dose = 50 mg/kg, the median survival time of treated group/control group (T/C) greater than 330%, cure = 5/6).

Novel indolo[3,2-b]quinolines (1d-g), introduced at the 7-position with an N-glycosylamino group, were prepared and their antitumor activities against leukemia P388 in mice were examined. The N-Galactopyranosylamino derivative (1e) was a much more potent anti-leukemia compound (optimal dose = 25 mg/kg, T/C greater than 333%, cure 5/6) than lead compound 1a.

Some tetracyclic quinolines (9 and 14) with a [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino side chain were prepared and their deoxyribonucleic acid (DNA) intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. The indoloquinoline derivative 9 exhibited the most potent activity (dose = 6.3 mg, T/C% = 300) in this series. The steric structural features of the chromophores of the compounds previously and newly synthesized were studied by a computer-associated molecular graphics technique. Relationships between the steric structural features of the chromophores and biological activities are also discussed.

Several fused tri- and tetracyclic quinolines (I and II) with [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino or [3-(N,N-dimethylamino)propyl]amino side chains were prepared, and their DNA intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. Some compounds having both intercalative ability and KB cytotoxicity were found to be inactive in vivo. However, a positive correlation was seen between the ability to induce topoisomerase II dependent DNA cleavage and antitumor activity in vivo. The indeno- (13a), benzofuro- (21a), and benzothieno- (22a) quinoline derivatives exhibited potent antitumor activities in vitro and in vivo, comparable to those of m-AMSA. They also intercalate DNA and induce topoisomerase II dependent DNA cleavage. Extended screening of 13a showed it to be active against solid tumors such as M5076 sarcoma, B16 melanoma, and colon 38 carcinoma.