Browsing by Author "Bastow, K.F."
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Item Antitumor agents. 250. design and synthesis of new curcumin analogues as potential anti-prostate cancer agents(Journal of Medicinal Chemistry, 2006) Lin, L.; Shi, Q.; Nyarko, A.K.; Bastow, K.F.; Wu, C.; Su, C.; Lee, K.In a continuing study of curcumin analogs as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogs classified into four series: monophenyl analogs (series A), heterocycle-containing analogs (series B), analogs bearing various substituents on the phenyl rings (series C) and analogs with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells; seven only against LNCaP; and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogs with better anti-prostate cancer activity.Item Antitumor agents. 256. Conjugation of paclitaxel with other antitumor agents: evaluation of novel conjugates as cytotoxic agents(Bioorganic and Medical Chemistry Letter (17): 2894-8, 2007) Nakagawa-Goto, K.; Nakamura, S.; Bastow, K.F.; Nyarko, A. K.; Peng, C.Y.; Lee, F.Y.; Lee, K.H.Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 20- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL–CPT conjugates, 8–10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED50 = 14.8, 3.1, 19.4 nM compared with 55.5 nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8–10 are possible antitumor drug candidates, particularly for prostate cancer.Item Cytotoxic isoprenylated flavonoids from the roots of sophora flavescens.(Helvetica Chimica Acta, 2004) Ding, P.; Chen, D.; Bastow, K.F.; Nyarko, A.K.; Wang, X.; Lee, K.Three new flavonoids, which are isoprenylated by fused 2,2-dimethyl-3,4-dihydro-2H-pyran moieties, were isolated from the roots of Sophora flavescens and named flavenochromanes A–C (1–3). Their structures were elucidated by spectroscopic methods, including 2D-NMR techniques. Flavenochromane C (3) showed strong cytotoxic activity against A549 (lung carcinoma), 1A9 (ovarian carcinoma), KB (epidermoid carcinoma of the nasopharynx), and KB-Vin (drug-resistant variant KB) cell lines with IC50 values ≤1.7 μM, and significant activity against the MCF-7 (breast adenocarcinoma) cell line with an IC50 value of 3.6 μM. Flavenochromane B (2) displayed slightly lower inhibitory effects (IC50 3.2–6.9 μM) as compared with 3.