Evaluation of the potential antimutagenic activities of new compounds by Ames assay has been of great interest for the development of novel therapeutics for many diseases including cancer. Ten novel bichalcophenes with in vitro and in vivo broad spectrum activities against various microbial strains were investigated throughout the present study for their cytotoxic, antioxidant, and antimutagenic potential in a Salmonella reverse mutation assay system against sodium azide (NaN3) and benzo[a]pyrene (B[a]P). At nontoxic concentrations, all bichalcophenes alone or in combination with NaN3 (1 μg/plate) or B[a]P (20 μM) with S9 mix were not mutagenic. The bichalcophenes significantly reduced NaN3- and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions in a concentration-independent manner. However, the antimutagenic activity of bichalcophenes against B[a]P varied depending on the exposure regimen, being more effective under pre-exposure conditions. The antimutagenic activity was correlated with a high antioxidant activity that could promote the DNA repair system. Bichalcophenes are least likely to interfere with the microsomal bioactivation of B[a]P. Monocationic bichalcophenes were superior to the corresponding mononitriles as antimutagenic agents against both mutagens investigated, possibly due to the higher nucleophilic centers they have which could bind and protect the bacterial DNA. Three monocationic compounds were shown to have a strong anticancer activity against the 58 cell line. Based on the results of the present investigation, monocationic compounds (1, 4, and 5B) will be selected for further time consuming and costly chemoprevention studies in animal models.

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The discovery of anticancer agents paradigm has been shifted to natural resources to overcome the toxicity of many synthetic agents at early clinical stages. In the present study, the antimutagenic, anticancer, phytochemistry, and free radical scavenging activities of five extracts of Conyza triloba were investigated. Extracts II (water : methanol), III (methylene chloride), and IV (methylene chloride : methanol) had the highest chlorophyll content and the highest superoxide scavenging, and metal chelating activities comparable to that of trolox. They also showed DPPH• scavenging activities better than that of α-tocopherol. Virtually all extracts exerted a strong (>40% reduction) antimutagenic activity against sodium azide and benzopyrene. Extracts II, III, and IV showed a remarkable growth inhibition profile with GI50 of 0.07–0.87 μg for Hepa1c1c7 and H4IIE1, A549, HT29, and PC3 cell lines and totally abated the growth of all cell lines, except for the breast cells, at 0.3–7.0 μg. The present study found a strong correlation between the chlorophyll content of Conyza extracts and their DDPH scavenging, metal chelating, and in vitro cytotoxic and cytostatic activities most probably through triggering apoptosis. This study could offer a platform for future studies and help selecting the vital features that identify the extract with potential anticancer activities.

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The therapeutic efficacy of two novel bifurans and vancomycin in an animal model of a methicillin-resistant Staphylococcus aureus (MRSA) infection was compared. Adult male CF-1 mice (25–35 g) were intraperitoneally injected with 200 μL/mouse containing 107 cell-forming units of MRSA. After 16 hours, animals were treated with 110 mg/kg of vancomycin, or 5 mg/kg of mononitrile bifuran (1A) or monocationic bifuran (1B) and killed after 8 hours. Treatment with bifurans did not cause any toxicity. Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen. Colonies recovered from livers and kidneys of mice injected with 1A or 1B lost the initial resistance pattern and became susceptible to methicillin and ciprofloxacin. MRSA elevated the serum urea level and activities of alanine aminotransferase and γ-glutamyl transpeptidase. MRSA also elevated the hepatic level of malondialdehyde, and serum levels of tumor necrosis factor and interleukin-6. MRSA also reduced the glutathione content and activities of catalase and glutathione S-transferase in liver. Similar to vancomycin, bifurans ameliorated most of the previous effects. Compound 1B was superior to 1A, and sometimes both provided better antistaphylococcal agents than vancomycin against MRSA pathogenesis. The present findings along with our previous studies support further evaluation of the efficacy of these bifurans in clinical studies.