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Quassinoids are highly oxygenated triterpenes, which were isolated as bitter principles from the plants of Simaroubaceae family. Their synthesis has attracted much attention because of the wide spectrum of their biological properties. The most prevalent quassinoids have C-20 picrasane skeleton, some known as bruceolides as they were isolated from the genus Brucea, which showed marked antileukemic and antimalarial activities.

We report in vitro antimalarial activities against chloroquine sensitive and resistant Plasmodium falciparum strains, and in vivo activities against Plasmodium berghei in mice for four series of ring-substituted- l -histidines and histamines.

Regiospecific synthesis of 2,3-disubstituted- l -histidines and 2,3-disubstituted histamines starting from l -histidine methyl ester and histamine is reported. The key step involves homolytic free radical alkylation via silver catalyzed oxidative decarboxylation of alkylcarboxylic acids with ammonium persulfate.

To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two compounds, where C-2 position of the antimalarial drug primaquine is blocked by metabolically stable bulky alkyl group are synthesized. Compound 2 [R = C(CH(3))(3)] of the series has produced excellent antimalarial efficacy against P. berghei and highly virulent multidrug-resistant P. yoelii nigeriensis strain in vivo. Compound 2 was also evaluated for methemoglobin (MetHb) toxicity. This study describes the discovery of a highly potent blood-schizontocidal antimalarial analogue 2, completely devoid of MetHb toxicity.

Regiospecific synthesis of 2,3-disubstituted- l -histidines and 2,3-disubstituted histamines starting from l -histidine methyl ester and histamine is reported. The key step involves homolytic free radical alkylation via silver catalyzed oxidative decarboxylation of alkylcarboxylic acids with ammonium persulfate.

We report in vitro antimalarial activities against chloroquine sensitive and resistant Plasmodium falciparum strains, and in vivo activities against Plasmodium berghei in mice for four series of ring-substituted- l -histidines and histamines.

We report in vitro antimycobacterial properties of ring-substituted quinolines (series 1-4) constituting 56 analogues against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains. The most effective compounds 2h (R1 = R2 = c-C6H11, R3 = NO2, series 1) and 13g (R1 = OC7H15, R2 = NO2, series 4) have exhibited an MIC value of 1 microg/mL against drug-sensitive M. tuberculosis H37Rv strain that is comparable to first line anti-tuberculosis drug, isoniazid. Selected analogues (2d, 2g, 2h, 4e, 6b, 13b, 13g, and 14e, MIC:or = 6.25 microg/mL) upon further evaluation against single-drug-resistant (SDR) strains of M. tuberculosis H37Rv have produced potent efficacy in the range between 6.25 and 50 microg/mL.

Thirteen new analogues (32-40, 45-48) of recently discovered potent blood-schizontocidal antimalarial agent, 2-tert-butylprimaquine (2) are synthesized and evaluated for in vivo antimalarial activities against drug-sensitive P. berghei strain and multi-drug resistant P. yoelii nigeriensis strain. Two of the amino acid conjugates (47-48) have exhibited potent antimalarial activities similar to that of 2 against both drug-sensitive and multi-drug resistant strains.