arglabin and Neoplasms

Topics: Alemtuzumab; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Azathioprine; Benzamides; Bevacizumab; Cetuximab; Erlotinib Hydrochloride; Gefitinib; Humans; Imatinib Mesylate; Neoplasms; Phthalazines; Piperazines; Pyridines; Pyrimidines; Quinazolines; Quinolones; Rituximab; Sesquiterpenes; Sesquiterpenes, Guaiane; Trastuzumab

Diverse amino analogs of Ludartin, a cytotoxic guaianolide and a position isomer of an anticancer drug, Arglabin were prepared through Michael type addition at its highly active α-methylene-γ-lactone motif. The semisynthetic derivatives were subjected to sulphorhodamine B cytotoxicity assay against a panel of four different human cancer cell lines viz. lung (A-549), leukemia (THP-1), prostate (PC-3) and colon (HCT-116) to look into structure-activity relationship. Few of the analogs displayed potent selective cytotoxicity compared to the parent molecule-Ludartin (1). (11R)-13-(Diethyl amine)-11,13-dihydroludartin (6) and (11R)-13-(piperidine)-11,13-dihydroludartin (10) showed almost same cytotoxicity against leukemia cell lines (THP-1) as that of parent molecule-Ludartin, but were more active against colon (HCT-116) cancer cells. (11R)-13-(Morpholine)-11,13-dihydroludartin (11) displayed selectively better cytotoxicity against Leukemia cancer cells (THP-1) exhibiting IC50 of 2.8 μM. (11R)-13-(6-Nitroindazole)-11,13-dihydroludartin (17) was four times more potent than Ludartin with selective cytotoxic effects against prostate cancer cells (2.2 μM) while as (11R)-13-(6-nitroindazole)-11,13-dihydroludartin (18) exhibited three-fold selective cytotoxicity for Lung (A-549) cancer cell lines exhibiting IC50 of 2.6 μM.

Topics: Amines; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Cytotoxins; Drug Screening Assays, Antitumor; Humans; Neoplasms; Sesquiterpenes; Sesquiterpenes, Guaiane; Structure-Activity Relationship

Arglabin derivatives varied at the endo- or exo-cyclic double bond were synthesized and studied in a colorimetric sulforhodamine B assay for their cytotoxicity. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α-methylene-γ-butyrolactone moiety led to compounds of similar or only slightly reduced cytotoxicity but different, cell line-dependent selectivity. In addition, arglabin is an excellent starting material for the synthesis of the guaianolide arborescin.

Topics: Antineoplastic Agents; Cell Line, Tumor; Colorimetry; Drug Screening Assays, Antitumor; Humans; Neoplasms; Rhodamines; Sesquiterpenes; Sesquiterpenes, Guaiane; Structure-Activity Relationship