18268-68-3Relevant articles and documents
Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics
Nilchan, Napon,Phetsang, Wanida,Nowwarat, Taechin,Chaturongakul, Soraya,Jiarpinitnun, Chutima
, p. 5343 - 5348 (2018/05/25)
Incorporation of halogen atoms to drug molecule has been shown to improve its properties such as enhanced in membrane permeability and increased hydrophobic interactions to its target. To investigate the effect of halogen substitutions on the antibacterial activity of trimethoprim (TMP), we synthesized a series of halogen substituted TMP and tested for their antibacterial activities against global predominant methicillin resistant Staphylococcus aureus (MRSA) strains. Structure-activity relationship analysis suggested a trend in potency that correlated with the ability of the halogen atom to facilitate in hydrophobic interaction to saDHFR. The most potent derivative, iodinated trimethoprim (TMP-I), inhibited pathogenic bacterial growth with MIC as low as 1.25 μg/mL while the clinically used TMP derivative, diaveridine, showed resistance. Similar to TMP, synergistic studies indicated that TMP-I functioned synergistically with sulfamethoxazole. The simplicity in the synthesis from an inexpensive starting material, vanillin, highlighted the potential of TMP-I as antibacterial agent for MRSA infections.
Synthesis and antitumor activity of feruloyl and caffeoyl derivatives This paper is dedicated to Prof. Wei-xiao Hu for his lifelong commitment to mentoring graduate students
Chen, Hui-Zhen,Chen, You-Bao,Lv, Ya-Ping,Zeng, Fang,Zhang, Juan,Zhou, Yong-Lie,Li, Han-Bing,Chen, Li-Fei,Zhou, Bin-Jie,Gao, Jian-Rong,Xia, Chun-Nian
supporting information, p. 4367 - 4371 (2015/02/06)
We developed two efficient protocols for the synthesis of feruloyl and caffeoyl derivatives from commercial vanillin and veratraldehyde. Pharmacological activities were assessed against a panel of human cancer cell lines in vitro. Most synthesized compounds demonstrated attractive cytotoxicity. Several new compounds demonstrated significant antiproliferative and cytotoxic activities against HeLa and Bewo tumor cell lines. In particular, 5-nitro caffeic adamantyl ester showed broad spectrum of tumor inhibition in 10 cell lines, and reduced tumor weight by 36.7% in vivo when administered at a dose of 40 mg kg-1.
Antineoplastic agents. 509. Synthesis of fluorcombstatin phosphate and related 3-halostilbenes
Pettit, George R.,Minardi, Mathew D.,Rosenberg, Heidi J.,Hamel, Ernest,Bibby, Michael C.,Martin, Sandie W.,Jung, M. Katherine,Pettit, Robin K.,Cuthbertson, Timothy J.,Chapuis, Jean-Charles
, p. 1450 - 1458 (2008/12/22)
The present SAR study of combretastatin A-3 (3a) focused on replacement of the 3-hydroxyl group by a series of halogens. That approach with Z-stilbenes resulted in greatly enhanced (> 10-100-fold) cancer cell growth inhibition against a panel of human cancer cell lines and the murine P388 lymphocytic leukemia cell line. Synthesis of the 3-fluoro-Z-stilbene designated fluorcombstatin (11a) and its potassium 3′-O-phosphate derivative (16c) by the route 7 → 8a → 11a → 14 → 16c illustrates the general synthetic pathway. The 3′-O-phosphoric acid ester (15) of 3-bromo-Z-stilbene 13a was also converted to representative cation salts to evaluate the potential for improved aqueous solubility, and the potassium salt (16 mg/mL in water) proved most useful. The fluoro (11a), chloro (12a), and bromo (13a) halocombstatins were nearly equivalent to combretastatin A-4 (1a) as inhibitors of tubulin polymerization and of the binding of colchicine to tubulin. The tubulin binding in cell-free systems was also retained in human umbilical vein endothelial cells. All three halocombstatins retained the powerful human cancer cell line inhibitory activity of combretastatin A-4 (1a) and proved superior to combretastatin A-3 (3a). In addition, the halocombstatins targeted Gram-positive bacteria and Cryptococcus neoformans.