Tumor anti-initiating activity of some novel 3,4-dihydropyrimidinones.

Halting the tumor initiation process by targeting the inhibition of the carcinogens metabolic activators (CYP), the induction of the carcinogen detoxification enzymes (glutathione-S-transferases, GSTs), and the induction of antioxidant activity is an effective strategy. Since several dihydropyrimidine derivatives (Biginelli compounds) are therapeutically active, the present study aimed to synthesize some dihydropyrimidines with multifunctional aromatic substitutions and to investigate their effects as anti-initiating agents. Twelve compounds were synthesized and structurally elucidated.

Synthesis and characterization of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-labeled fluorescent ligands for the mu opioid receptor.

A series of opioid ligands utilizing the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene++ +-3-propionic acid or 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza- s-indacene-3-propionic acid were synthesized and characterized for their ability to act as a suitable fluorescent label for the mu opioid receptor. All compounds displaced the mu opioid receptor binding of [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol in monkey brain membranes with high affinity. The binding of fluorescent ligands to delta and kappa receptors was highly variable.

Identification of kappa opioid receptors in the immune system by indirect immunofluorescence.

A method to visualize the kappa opioid receptor is described that uses a high-affinity fluorescein-conjugated opioid ligand and indirect immunofluorescence with the phycoerythrin fluorophore to amplify the signal. The mouse thymoma cell line R1E/TL8x.1.

N-methylcarbamate derivatives of ellipticine and olivacine with cytotoxic activity against four human lung cancer cell lines.

A series of analogues of the antitumor alkaloids ellipticine and olivacine were tested for cytotoxicity against four human lung cancer cell lines: H69, N417, H460, and H358. Adriamycin (doxorubicin), ellipticine, olivacine, and celiptinium were used as standards. Adriamycin was cytotoxic at 2 microM and celiptinium was inactive at the highest concentrations tested (IC50 > 48 microM).

Mode of action of the schistosomicide hycanthone: site of DNA alkylation.

Condensation of hycanthone N-methylcarbamate (HNMC) with deoxyguanosine (dG) furnished a mixture of the N-1 and N2 adducts which were purified and characterized as their acetates. Condensation of HNMC with thymidine (T) gave the N-3 adduct in poor yield. Adenosine (A) and cytidine (C) did not react with HNMC.

Studies on some derivatives of oxamniquine.

On the basis of the remarkable biological similarities between hycanthone and oxamniquine and as a sequel to our finding that some esters of hycanthone are active against hycanthone-resistant schistosomes, we prepared oxamniquine acetate, oxamniquine N-methylcarbamate, and four substituted phenylsulfonohydrazones of oxamniquine aldehyde. These compounds were tested for their effect on survival of and on [3H]uridine incorporation into hycanthone-sensitive and -resistant Schistosoma mansoni. All of these derivatives were effective to a greater or lesser degree in killing worms and in inhibiting [3H]uridine incorporation in the sensitive strain, but none was effective in the resistant strain.