[Show abstract][Hide abstract] ABSTRACT: A variety of diazepinone derivatives were prepared from α-amino acids and amino alcohols by a new synthetic methodology based on ring closing metathesis as a key step. The diazepinones were coupled with ribose derivatives to afford novel diazepinone nucleosides. Among them, (4R)-1-ribosyl-4-methyl-3,4-dihydro-1H-1,3-diazepin-2(7H)-one () showed a potent inhibitory effect (K(i) = 145.97 ± 4.87 nM) against human cytidine deaminase.
Chemical Communications 10/2012; 48(93). DOI:10.1039/c2cc35484e · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The natural products moracins O and P exhibited potent in vitro inhibitory activity against hypoxia-inducible factor (HIF-1), which is a key mediator during adaptation of cancer cells to tumour hypoxia. Systematic variations of the structures of benzofuran type moracins were made and structure-activity relationship analysis showed the importance of the 2-arylbenzofuran ring and the (R)-configuration of the core scaffold. Further evaluation of the representative compound 5 showed its inhibitory effect on HIF-1α protein accumulation and target gene expression under hypoxia.
European Journal of Medicinal Chemistry 06/2011; 46(6):2386-96. DOI:10.1016/j.ejmech.2011.03.022 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect.
[Show abstract][Hide abstract] ABSTRACT: The first total synthesis of the naturally occurring benzofurans, moracins O and P was achieved using a Sonogashira cross coupling reaction followed by in situ cyclization, and the absolute configuration of natural moracin O was established.
Chemical Communications 05/2009; DOI:10.1039/b823340c · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A series of amide and urea derivatives of benzothiazole have been synthesized and evaluated for their antiproliferative profile in human SK-Hep-1 (liver), MDA-MB-231 (breast), and NUGC-3 (gastric) cell lines. Among them, compounds 1-2, 16-18, 23, and 25-26 had potent to moderate inhibitory activities. Further these compounds were investigated for their ability to inhibit Raf-1 activity.
European Journal of Medicinal Chemistry 08/2008; 43(7):1519-24. DOI:10.1016/j.ejmech.2007.10.008 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new series of geldanamycin derivatives were synthesized using a semi-synthetic approach involving genetically engineered biosynthetic intermediates. These analogues were then evaluated for anti-proliferation activity in human cancer cell lines, SK-Br3 and SK-Ov3. Most of the synthesized compounds exhibited potent in vitro anti-proliferation activity toward both cell lines. Such compounds potently inhibited the expression of the Hsp90 client protein ErbB2.