Kuan-Han Lee

Synthesis and Cytotoxic Evaluation of a Series of γ-Substituted γ-Aryloxymethyl-α-methylene-γ-butyrolactones Against Cancer Cells

AbstractPurpose. The main objective of this investigation was to explore thecytotoxic structure-activity relationships of γ-substituted γ-aryloxymethyl-α-methylene-γ-butyrolactones against cancer cells. Methods. The target compounds were synthesized in two stepscommencing with aryl-OH which was treated with a bromomethyl ketonefollowed by the Reformatsky-type condensation. Results. Seven types of α-methylene-γ-butyrolactones were evaluatedin vitro against 60 human cancer cell lines derived from nine cancercell types. The average values of log G50 indicated that for thearylportion, potencies of these α-methylene-γ-butyrolactones are in adecreasing order of quinolin-2(1H)-one (or 2-hydroxyquinoline, 21,−5.89) > quinoline (19, −5.79) > 2-methylquinoline (20, −5.69)> 8-hydroxyquinoline (17, −5.64) > 2-naphthalene (16, −5.59)> benzene (15, −4.90). The same order was obtained for both log TGIand log LC50. However, for the γ-substituent, the potencies are in adecreasing order of biphenyl (16f–21f) > phenyl and4-substituted phenyl (16b-e–21b-e) > methyl (16a–21a). Conclusions. Unlike cardiovascular activities of α-methylene-γ-butyrolactones in which a γ-methyl substituent is necessary for vasorelaxingeffect while a phenyl or a halogen-substituted phenyl is prefer for theantiplatelet activities, a γ-biphenyl substituent proved to be the bestfor their cytotoxicities against various cancer cell lines tested.

Synthesis and anticancer evaluation of certain γ-aryloxymethyl-α-methylene-γ-phenyl-γ-butyrolactones

Certain gamma-aryloxymethyl-alpha-methylene-gamma-phenyl- gamma-butyrolactones were synthesized and evaluated for their anticancer activity. These compounds demonstrated a strong growth inhibitory activity against leukemia cell lines but are relatively inactive against non-small cell lung cancers and CNS cancers. The anticancer potency for aryl portion is in an order of quinoline > 8-hydroxyquinoline > 2-methylquinoline >> naphthalene >> benzene.

Synthesis and anticancer evaluation of certain α-methylene-γ-(4-substituted phenyl)-γ-butyrolactone bearing thymine, uracil, and 5-bromouracil

Certain α-methylene-γ-(4-substituted phenyl)-γ-butyrolactone bearing thymine, uracil, and 5-bromouracil were synthesized and evaluated for their anticancer activity. These compounds demonstrated a strong growth inhibitory activity against leukemia cell lines. The anticancer potency for the substituents of the lactone C(γ)-phenyl is in an order of 4-Ph > 4-Cl, 4-Br > 4-Me, 4-NO2 > 4-F. For the pyrimidine portion, 5-bromouracil is more potent than uracil and thymine.

Synthetic and Antiviral Studies on Certain Acyclic Nucleosides of 5-Benzyl-6-Azauracil Derivatives

Abstract Several 5-(4-substituted benzyl)-6-azauracils have been synthesized from the corresponding benzaldehydes. The 5-benzyl-6-azauracils were silylated with hexamethyldisilazane and then glycosylated with aliphatic halides, e.g., (2-acetoxyethoxy)methyl bromide and 1,3-dibenzyloxy-2-chloromethoxypropane, to give protected acyclic nucleosides which were deprotected to afford acyclonucleosides of 5-(4-substituted benzyl)-6-azauracils. None of the compounds exhibited significant antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro.

Synthetic and Antiviral Studies of Certain Acyclic 3′-Azido-3′-Deoxythymidine (AZT) Analogues

Abstract A direct alkylation of trimethylsilylated pyrimidines and azapyrimidines with 1-azido-3-benzyloxy-2-chloromethoxypropane gave acyclic analogues of AZT in a good overall yield. None of the compounds exhibited significant antiviral activity against human immunodeficiency virus and herpes simplex virus.

Condensed as-triazine II: Synthesis of 7-phenyldihydro- and tetrahydropyrazino-[2,3-e]-as-triazines

Certain derivatives of dihydro- and tetrahydropyrazino[2,3-e]-as-triazines were prepared by ring closure of 5,6-diamino-as-triazines with phenylglyoxal in methanol. These 4-azapteridines experience an addition of the alcohol at C(7), and N(8) underwent an unusual methylation under acidic conditions affording the 7-methoxy-8-methyl-6-phenyldihydropyrazino derivative. Regioselective control by the aldehyde-binding reagent, sodium hydrogen sulfite and sodium sulfite, tends to direct the phenyl group to the C(7). Hinsberg reaction of 5,6-diamino-as-triazines with phenacyl bromide proceeded in regiospecific fashion to give the E-form Schiff bases which then isomerize to the corresponding enamines

An intermolecular Michael addition of benzene

Abstract The first intermolecular Michael addition of benzene leading to the formation of 3,3-diphenylpropionanilide is described. 2-Methoxyaniline was reacted with cinnamoyl chloride to give 2-methoxycinnamanilide ( 1 ) which was treated with aluminum chloride in benzene at 80°C to afford 2′-hydroxy-3,3-diphenylpropionanilide ( 4 ) in an 85% overall yield. Accordingly, 4′-hydroxy-2′-methyl-3,3-diphenylpropionanilide ( 6 ) was prepared from 4-methoxy-2-methylcinnamanilide ( 5 ) in 76% yield.