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Synthesis of a cytotoxic dihydrochalcone, first isolated from a traditional Amazonian medicinal plant Iryanthera juruensis Warb (Myristicaceae), followed by a comprehensive SAR analysis of saturated and unsaturated chalcone synthetic intermediates, led to the identification of analogues with selective and significant in vitro anti- Trypanosoma cruzi activity. Further SAR studies were undertaken with the synthesis of 21 new chalcones containing two allyloxy moieties that resulted in the discovery of 2',4'-diallyloxy-6'-methoxy chalcones with improved selectivity against this parasite at concentrations below 25 microM, four of which exhibited a selectivity index greater than 12.

The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay of the ether, methanol, and aqueous extracts of the spice Myristica malabarica (rampatri) revealed the methanol extract to possess the best antioxidant activity. Column chromatography of the methanol extract led to the isolation of a new 2-acylresorcinol and four known diarylnonanoids of which the diarylnonanoid, malabaricone C, showed the maximum DPPH scavenging activity. Malabaricone C could prevent both Fe(II)- and 2,2'-azobis(2-amidinopropane)dihydrochloride-induced lipid peroxidation (LPO) of rat liver mitochondria more efficiently than curcumin. The anti-LPO activity of malabaricone C was attributed to its better radical scavenging and Fe(II) chelation capacities. The superior activity of malabaricone C was rationalized by a systematic structure-activity correlation of the results obtained with the structurally related diarylnonanoids and curcumin. Malabaricone C also prevented the gamma-ray-induced damage of pBR322 plasmid DNA in a concentration-dependent manner. The radioprotective activity was found to correlate with its (*)OH radical scavenging property, which matched well with that of d-mannitol.

The first stereoselective total synthesis of the naturally occurring flavan myristinin A has been accomplished, as well as its biochemical evaluation. This synthesis verified the structural assignment and allowed for the determination of the absolute stereochemistry. Myristinin A exhibits biochemical activity both as a potent DNA-damaging agent and DNA polymerase beta inhibitor. Relaxation of supercoiled plasmid DNA was observed at picomolar concentrations, in addition to inhibition of polymerase beta at low micromolar concentrations.

The first naturally occurring atropisomeric flavans, myristinins B (2), C (2a), E (4), and F (4a), together with their corresponding trans-isomers, myristinins A (1) and D (3), were isolated from the CH(2)Cl(2) extract of Myristica cinnamomea fruits. Compounds 1, the mixture of 2 and 2a, and the mixture of 4 and 4a, exhibited antifungal activity against Candida albicans with IC(50) values ranging from 5.9 to 8.8 microg/mL, and they selectively inhibited the enzyme cyclooxygenase-2 (COX-2).

Acid-catalyzed cyclizations of E,E-dibenzylidenesuccinate esters have been developed as an efficient synthetic route to 1-aryl-1,2-dihydronaphthalenes. This reaction has been used in the synthesis of the naturally occurring lignans (+/-)-cagayanin and (+/-)-galbulin.