Antimycobacterial activity of 4'-bromo-[1,1'-biphenyl]-4-yl 4-x-phenylmethanone derivatives, and their acute toxicity and cytotoxicity.

The antimycobacterial activity of nine biphenyl methanone (BPM) derivatives against standard strains of Mycobacterium kansasii, M. avium and M. malmoense was determined by colorimetric assay in microplates with the dye Alamar Blue. Acute toxicity of these compounds was also analyzed by determination of CO2 concentration in a respirometric assay using Escherichia coli. The compounds showed weak antimycobacterial activity with a minimal inhibitory concentration (MIC) over 0.038 mmol l-1 and no toxicity was found in E. coli up to 400 mmol l-1. No cytotoxicity was observed on V79 cells up to 0.35 mmol l-1 with 7 of the BPM derivatives, with two exceptions (X = SO2CH3, NO2) that showed some toxicity. The greatest antimycobacterial activity was observed with the SO2CH3 derivative and the application of Principal Component Analysis (PCA) showed a relationship between structure and antimycobacterial activity of the compounds. Two descriptors, nucleophilic superdelocalizability of carbon atom and pi-hydrophobic constant, were necessary to describe this relationship.

Evaluation of in vitro toxicity of N,N-dimethyl-2-propen-1-amines isomers.

The trypanocidal activities of cis-3-(4'-bromo[1,1'-biphenyl]-4-yl)- 3-(phenyl)-N,N-dimethyl-2-propen-1-amine (Vb) and cis-3-(4'-bromo[1,1'-biphenyl]-4-yl)-3-(4-bromophenyl)-N,N-dimethyl-2- propen-1-anine (Vg) appeared 6.3 and 3.5 fold more active than the trans-isomers, respectively. Multi-endpoints for toxicity were also applied. Neutral red uptake (NRU), tetrazolium salt reduction (MTT), DNA content on V79 fibroblast cell culture and acute toxicity von E. coli were measured. The IC50 through DNA contents was lower for the cis-isomers in both series of compounds 5b: 7.8 microM and 5g: 5.2 microM). NRU values for derivative 5b in isomeric mixture shows the same value as the isolated isomers however, in the case of 5g a more significant toxicity of the cis-isomer was found. MTT values show that 5g is more toxic than 5b. In both cases, the acute toxicity of the trans-isomers was higher than that of the cis-isomers.

Efficacy of hyperthermic isolated limb perfusion for extremity-confined recurrent melanoma.

BACKGROUND: Recurrent melanoma of the extremity has been treated by local excision, systemic chemotherapy, amputation, or a combination of these approaches. Hyperthermic isolated limb perfusion (HILP) provides a method of limb preservation through isolation, allowing the administration of chemotherapy in higher doses than is possible through systemic treatment. METHODS: An experimental group of 59 HILP patients with melanoma recurrences of the extremity was studied prospectively. A control group of 248 melanoma patients with similar recurrences was excluded from HILP because their recurrences were in non-extremity locations. The experimental group underwent HILP and excision; the control group had excision only. The experimental procedure consisted of vascular isolation of the affected extremity and a 1-hour perfusion with melphalan. Temperatures were maintained at 40 degrees C in the perfusion circuit. RESULTS: The HILP patients had a lower rate of locoregional recurrence (P=.028) and demonstrated increased survival (P=.026) compared to the control group. In multivariate regression analysis, which included age, ulceration and thickness of the primary, and the treatment variable of perfusion, age (P=.02) and perfusion for the treatment of recurrence (P=.006) were significant predictors of survival. CONCLUSIONS: HILP improves prognosis by sterilizing the treated extremity, controlling locoregional disease, and perhaps preventing metastasis, thus having a positive impact on overall survival.

In vitro trypanocidal activities of a novel series of N, N-dimethyl-2-propen-1-amine derivative.

The trypanocidal activity of several 3-(4'-bromo-[1,1-biphenyl]-4-yl) -3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine derivatives of the three evolutionary stages of Trypanosoma cruzi, namely the bloodstream trypomastigote form and both the proliferative epimastigote and amastigote forms, were studied. For both proliferative forms of T. cruzi, total lysis occurred at 10-60 microM for trypomastigotes at 40-200 muM. The following order of susceptibility was established: amastigotes > epimastigotes > trypomastigotes. The most were the bromo (X = g) and unsubstituted (X = b) compounds, which had 13- and 8-fold higher activity against trypomastigotes, respectively, than nifurtimox. Cytotoxicity in the Chinese hamster V-79 cell line, measured as inhibition of cell proliferation showed that all the compounds had the same range of IC50 (7.0-12.4 muM). The halogen (X = a,g,h) and the unsubstituted derivatives (X = b) were the least toxic in the series together with the compound (X = f).