I. Isolation, via activity-directed fractionation, of mercaptobenzothiazole and dibenzothiazyl disulfide as two allergens responsible for shoe dermatitis. II. Bioactive constituents of Melodorum fruticosum Lour. (Annonaceae)

Jee Hyung Jung, Purdue University

Abstract

I. Shoe dermatitis is a delayed hypersensitivity reaction which results from exposure of sensitized individuals to contact allergens of shoe components. It is not a rare symptom, and the putative contact allergens mostly originate from the rubber parts of the shoes. One of the most frequent culprits from the rubber parts of the shoe are thiazoles which are used as an accelerator in the vulcanization process. In our case study the causative thiazoles were proven to be mercaptobenzothiazole and dibenzothiazyl disulfide; dibenzothiazyl disulfide was more active than mercaptobenzothiazole in patch tests on the patient. This is the first time that the tentative allergens of shoe dermatitis were revealed by directly extracting the troublesome shoe itself with fractionation guided by patch testing on the patient. II. In our search for natural antitumor compounds, the previously uninvestigated species, Melodorum fruticosum Lour. (= Unona dumetorum Dunal, Annonaceae), was examined. Guided by the simple brine shrimp larvae lethality assay, diverse bioactive known and novel compounds, including members of the flavonoids (pinocembrin, dichamanetin), triterpenes (polycarpol), plant sterols (stigmasterol, $\beta$-sitosterol), simple aromatics (benzylbenzoate), and heptenes (acetylmelodorinol, isomelodienone, melodienone, melodorinol, 6-hydro-7-hydroxymelodienone, homoisomelodienone, and homomelodienone) were isolated. Individual compounds were assayed for inhibition of crown gall tumors in the potato disc assay, the Lemna assay, human tumor cell culture assays (A-549, HT-29, MCF-7, SK-MEL-5, Malme-3M), murine tumor cell culture assay (9PS), and the protein tyrosine kinase assay. The heptenes isolated represent a new class of natural compounds and were generally cytotoxic to human tumor cell lines (ED$\sb{50}$ values in the 10$\sp{-1}$ $\mu$g/ml range). It is thought that the cytotoxicities of the heptenes are significant enough to attempt further antitumor bioassays. Polycarpol was interesting in its potent cytotoxicities toward the human tumor cell lines (A-549 5.45 $\times$ 10$\sp{-1}$ $\mu$g/ml, HT-29 1.27 $\times$ 10$\sp{-1}$ $\mu$g/ml, MCF-7 2.22 $\times$ 10$\sp{-1}$ $\mu$g/ml) and in its unexpected effect on the growth promotion of crown gall tumors (179/70% growth promotion).

Degree

Ph.D.

Advisors

McLaughlin, Purdue University.

Subject Area

Health|Agricultural chemicals|Oncology|Pathology

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