In vitro anti-uveal melanoma activity of phenolic compounds from the Egyptian medicinal plant Acacia nilotica.

Anti-uveal melanoma activity-guided fractionation of the MeOH extract of Acacia nilotica pods resulted in the isolation of the new compound gallocatechin 5-O-gallate in addition to methyl gallate, gallic acid, catechin, catechin 5-O-gallate, 1-O-galloyl-β-D-glucose, 1,6-di-O-galloyl-β-D-glucose and digallic acid. The structures of the isolated compounds were elucidated on the basis of HRESIMS, NMR spectroscopy and CD data. In addition to uveal melanoma, the antiproliferative activities of the isolated compounds and the related compound epigallocatechin 3-O-gallate (EGCG) were evaluated against cutaneous melanoma, ovarian cancer, glioblastoma and normal retinal pigmented cells.

Antiparasitic activity of C-geranyl flavonoids from Mimulus bigelovii.

Bioactivity-directed fractionation of the MeOH fraction of the extract of Mimulus bigelovii by means of an axenic Leishmania amastigote assay and chromatographic techniques resulted in the isolation of four C-geranyl flavanones, diplacone (1), 3'-O-methyldiplacone (2), 4'-O-methyldiplacone (3), 3'-O-methyldiplacol (4), together with a geranylated flavone, cannflavin A (5). These compounds were separated from M. bigelovii for the first time.

MET oncogene inhibition as a potential target of therapy for uveal melanomas.

PURPOSE. The purposes of this study were to investigate the frequency of MET activation in uveal melanomas (UMs), to study the potential molecular mechanism for its activation, and to assess the utility of MET inhibition as a potential therapy for UM. METHODS.

Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis.

Millions of people in the developing world are affected by diseases caused by the kinetoplastid parasites: the leishmaniases, African trypanosomiasis, and Chagas disease. In many cases the drugs employed for treatment are toxic, marginally effective, given by injection, and/or compromised by the development of resistance. Since safe, effective, and affordable chemotherapeutic agents for leishmaniasis and trypanosomiasis are clearly needed, the identification of new antikinetoplastid drug candidates should be an urgent priority.

Isoflavonoids and other compounds from Psorothamnus arborescens with antiprotozoal activities.

Bioactivity-guided fractionation of the root extract of Psorothamnus arborescens yielded the new isoflavone 5,7,3',4'-tetrahydroxy-2'-(3,3-dimethylallyl)isoflavone (1a) and the new 2-arylbenzofuran 2-(2'-hydroxy-4',5'-methylenedioxyphenyl)-6-methoxybenzofuran-3-carbaldehyde (2), together with seven known compounds, including three isoflavones, fremontin (3a), glycyrrhisoflavone (4a), and calycosin (5), two pterocarpans, maackiain (6) and 4-hydroxymaackiain (7), one triterpene, oleanolic acid (8), and one chalcone, isoliquiritigenin (9). In addition, the structure of the isoflavone fremontin was revised using spectroscopic and chemical methods and was assigned the new structure 3a. The isoflavone 1a and the chalcone 9 displayed leishmanicidal activity with IC50 values of 13.

Antiprotozoal compounds from Psorothamnus polydenius.

Bioactivity-guided fractionation of the methanolic extract of Psorothamnus polydenius yielded the new chalcone 2,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone (2), together with six other known compounds, 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (1), dalrubone (3), demethoxymatteucinol (4), eriodictyol (5), and photodalrubone (6a and 6b). This is the first report of chalcones in P. polydenius.

Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles.

A series of 5-thiocyanatomethyl- and 5-alkyl-3-aryl-1,2,4-oxadiazoles were synthesized and evaluated for their activity against kinetoplastid parasites. Formation of the oxadiazole ring was accomplished through the reaction of benzamidoximes with acyl chlorides, while the thiocyanate group was inserted by reacting the appropriate 5-halomethyl oxadiazole with ammonium thiocyanate. The thiocyanate-containing compounds possessed low micromolar activity against Leishmania donovani and Trypanosoma brucei, while the 5-alkyl oxadiazoles were less active against these parasites.

Synthesis and antitubulin activity of N1- and N4-substituted 3,5-dinitro sulfanilamides against African trypanosomes and Leishmania.

Thirty analogues of N(1)-phenyl-3,5-dinitro-N(4),N(4)-di-n-propylsulfanilamide (GB-II-5, compound 3), a new antikinetoplastid antimitotic agent, have been synthesized and evaluated. The addition of simple functional groups to the N1 aromatic ring generally decreases antiparasitic and antimitotic potency, but placement of a dibutyl substituent at the N4 nitrogen to give N(1)-phenyl-3,5-dinitro-N(4),N(4)-di-n-butylsulfanilamide (compound 35) augments antitrypanosomal and antileishmanial activity. Compound 35 possesses IC(50) values of 0.

The activity of diguanidino and 'reversed' diamidino 2,5-diarylfurans versus Trypanosoma cruzi and Leishmania donovani.

The in vitro activity of 20 dicationic molecules containing either diguanidino or reversed amidine cationic groups were evaluated versus Trypanosoma cruzi and Leishmania donovani. The most active compounds were in the reversed amidine series and six exhibited IC(50) values of less than 1 micro mol versus T. cruzi and five gave similar values versus L.

Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin.

Novel dinitroaniline sulfonamides based on the herbicide oryzalin 3 were synthesized and evaluated for activity against the parasitic protozoan Leishmania donovani and against leishmanial tubulin, the putative antiparasitic target of oryzalin. A subset of these compounds possess more activity against both Leishmania and the target protein in vitro. Compound 20 displays improved potency against leishmanial tubulin and is 13.