Inhibition of chitin synthesis by two 1-(2,6-disubstituted benzoyl)-3-phenylurea insecticides. II

Deul, D.H.; Jong, B.J. de; Kortenbach, J.A.M.

doi:10.1016/0048-3575(78)90096-2

Cited by 91 publications

(19 citation statements)

References 15 publications

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“…4s' Histological and biochemical examinations of affected larvae have revealed disturbances in the endocuticular matrix suggesting a defect in the process of endocuticular deposition. [7][8][9][10][11][12] Tobacco hornworm (Manduca sexta) larvae are ideal for a study of the action of these inhibitors of cuticle formation because the molting cycle is well-defined13) and the larval epidermis forms cuticle in vitro. 14,15) Therefore, in this paper the effects of diflubenzuron on chitin synthesis in Manduca larvae during the final instar will be examined.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Chitin Synthesis by Diflubenzuron in <i>Manduca</i> Larvae

et al. 1980

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Section: Introductionmentioning

confidence: 99%

Inhibition of Chitin Synthesis by Diflubenzuron in <i>Manduca</i> Larvae

et al. 1980

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“…Diflubenzuron (DFB), a pesticide, was the first of the benzoylphenyl ureas to be reported as a growth regulator [1,2], and might therefore inhibit tumor growth. The mode of action of DFB is unknown, but seems to be cell specific in the fruit fly for those cells originating from the epidermal histoblast [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Effects of benzoylphenyl ureas on growth of B16 melanoma cells in vitro and in vivo

Hofs¹,

McVie

1991

Invest New Drugs

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New analogs of diflubenzuron, a benzoylphenyl urea, are tested on their in vitro cytostatic activity against B16 melanoma cells. The following structure-activity relationship was established: substitution by a hydroxylated function at the ortho, meta or para position or by a dimethylamino function at the ortho position of the benzoyl moiety appeared to be necessary for cytostatic activity in vitro. Acetoxy functions at the ortho position or hydroxy functions at the para position of the aniline ring resulted also in active compounds. A number of these benzoylphenyl ureas are selected for in vivo evaluation of antitumor activity on B16 melanoma growing s.c.. Although many of the tested benzoylphenyl ureas delayed tumor growth during the first ten days of drug treatment, only a few increased animal life span. The best results (% T/C) were obtained with compounds 5 (127%), 7 (147%), 13 (135%) and 16 (135%), which all have hydroxylated functions in the benzoyl moiety.

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“…Although the means by which these compounds act have not been fully elucidated, diflubenzuron (DFB) which has the formula [1-(2,6-difluorobenzoyl)-3-(4-chlorophenyl) urea] inhibits chitin synthesis in insects (1)(2)(3)(4)(5), DNA synthesis in pupae of the stable fly (6), and proliferation and differentiation of primordial cells into the imaginal epidermis in insects (7). Further, there is evidence that DFB inhibits melanogenesis (8) and nucleoside uptake (9) in mouse melanoma cells.…”

Section: Introductionmentioning

confidence: 99%

Role of metabolism in effects of diflubenzuron on growth of B16 melanomas in mice

Jenkins¹,

Perry²,

Ahmed³

et al. 1986

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The insect growth regulator diflubenzuron (DFB), which also inhibits growth of experimental tumors in mice, was studied to determine the influence of in vivo microsomal metabolism on its antitumor activity. DFB inhibits chitin synthesis and growth of imaginal epidermis in insects and suppresses melanogenesis and uptake of nucleosides in mouse melanoma cells, but the means of cell growth regulation and the role of metabolism of DFB in such regulation have not been established. Five daily injections of DFB (total of 4000 mg/kg) into C57BL/6 mice with B16 melanomas induced an acute 11-20% decrease in tumor volume and a 2-3 day increase in the initial tumor volume doubling time (Td), but at mid-treatment tumors regained maximum (control-like) rate of volume increase. Tumors in mice conditioned with a mixed function oxidase inhibitor (CoCl2) and treated with DFB did not decrease in mean volume, but their rate of volume increase was reduced by about 75% and the Td was increased by 4.2 days. In contrast, induction of mixed function oxidase with 3-methylcholanthrene (3-MC) or beta-napthaflavone (B-NF) enhanced the effects of DFB by a factor of 1.5 to 2.0. Therefore, aromatic hydroxylation of DFB may be required for tumor growth regulation. Three metabolites of DFB--two hydroxylated forms and a scission product, 4-chlorophenylurea (CPU), were also tested for tumor growth regulation. CPU was ineffective; a form oxidized at the 3 carbon of the phenyl ring (3-OH-DFB) was only marginally effective; but the 2-carbon form (2-OH-DFB) induced a 24% decrease in mean tumor volume and a 2.4 day increase in Td. Pretreatment with 3-MC and treatment with 2-OH-DFB also resulted in a 24% decrease in tumor volume and a 2.2 day increase in Td, but also reduced tumor volume increase to 20% between the 5th and 10th days after the initial 2-OH-DFB injection, compared to a 125% increase without 3-MC. Further, 3-MC pretreatment caused the otherwise marginally effective 3-OH-DFB to become almost as effective as 2-OH-DFB. These data support our previous report that DFB alters tumor growth and show that mixed function oxidase enhances effects of DFB, 2-OH-DFB and 3-OH-DFB.

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Inhibition of chitin synthesis by two 1-(2,6-disubstituted benzoyl)-3-phenylurea insecticides. II

Cited by 91 publications

References 15 publications

Inhibition of Chitin Synthesis by Diflubenzuron in <i>Manduca</i> Larvae

Inhibition of Chitin Synthesis by Diflubenzuron in <i>Manduca</i> Larvae

Effects of benzoylphenyl ureas on growth of B16 melanoma cells in vitro and in vivo

Role of metabolism in effects of diflubenzuron on growth of B16 melanomas in mice

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