206649-07-2Relevant articles and documents
Design, synthesis and biological evaluation of combretastatin A-4 sulfamate derivatives as potential anti-cancer agents
Huang, Jinwen,Huang, Leilei,Li, Yingzi,Nie, Hui,Song, Lixing,Wu, Fanhong
supporting information, p. 1374 - 1380 (2021/09/30)
A series of combretastatin A-4 (CA-4) sulfamate derivatives were synthesized and their structure-activity relationship on tubulin, arylsulfatase and tumor cell antiproliferation inhibition was studied. Among them, compound 16a showed excellent potency as well as CA-4 under the same conditions against six tumor cells including HTC-116, HeLa, HepG2, MGC803, MKN45 and MCF-7 cells, respectively. Molecular docking revealed that several important hydrogen bond interactions were formed between the sulfamate group of 16a and the colchicine binding site of tubulin and steroid sulfatase respectively. Although compound 16a was less active than CA-4 in regard to its in vitro activity as an inhibitor of tubulin polymerization, it was effective as an inhibitor of arylsulfatase. This novel combretastatin A-4 sulfamate derivative has the potential to be developed as a dual inhibitor of tubulin polymerization and arylsulfatase for cancer therapy.
Design, Synthesis, and in vitro and in vivo Evaluations of (Z)-3,4,5-Trimethoxystyrylbenzenesulfonamides/sulfonates as Highly Potent Tubulin Polymerization Inhibitors
Mahesh, Rasala,Nayak, Vadithe Lakshma,Babu, Korrapati Suresh,Riyaz, Syed,Shaik, Thokhir Basha,Kumar, Gajjela Bharth,Mallipeddi, Prema Latha,Reddy, Challa Ratna,Shekar, Kunta Chandra,Jose, Jedy,Nagesh, Narayana,Kamal, Ahmed
, p. 678 - 700 (2017/05/15)
Newer therapeutics can be developed in drug discovery by adopting the strategy of scaffold hopping of the privileged scaffolds from known bioactive compounds. This strategy has been widely employed in drug-discovery processes. Structure-based docking studies illustrate the basic underlying concepts and reveal that interactions of the sulfonamide group and hydrophobic interactions are crucial. On the basis of this strategy, over 60 synthetic analogues were synthesized and evaluated for their cytotoxicity against the NCI panel of 60 human cancer cell lines; the majority of these compounds exhibited promising cytotoxicity with GI50 values ranging between 18 and 50 nm. Among these compounds, (Z)-N-[2,3-dimethoxy-5-(3,4,5-trimethoxystyryl)phenyl]-4-methoxybenzenesulfonamide (7 a) and (Z)-N-[2-hydroxy-3-methoxy-6-(3,4,5-trimethoxystyryl)phenyl]-4-methoxybenzenesulfonamide (9 a) were found to be potent. Similar results were obtained against three human cancer cell lines with IC50 values ranging between 0.04 and 3.0 μm. Studies aimed at elucidating the mechanism of action of these new analogues revealed that they inhibited the in vitro polymerization of tubulin and disorganized the assembly of microtubules in HeLa and MCF-7cancer cells. Lead compounds 7 a and 9 a displayed notable in vivo antitumor activity in a HeLa tumor xenograft model. Our studies have resulted in the identification of a scaffold that can target tubulin polymerization, which should have significant potential toward the development of new antitumor drugs.
Combretastatin A-4 and Derivatives: Potential Fungicides Targeting Fungal Tubulin
Ma, Zhong-Lin,Yan, Xiao-Jing,Zhao, Lei,Zhou, Jiu-Jiu,Pang, Wan,Kai, Zhen-Peng,Wu, Fan-Hong
, p. 746 - 751 (2016/02/10)
Combretastatin A-4, first isolated from the African willow tree Combretum caffrum, is a tubulin polymerization inhibitor in medicine. It was first postulated as a potential fungicide targeting fungal tubulin for plant disease control in this study. Combretastatin A-4 and its derivatives were synthesized and tested against Rhizoctonia solani and Pyricularia oryzae. Several compounds have EC50 values similar to or better than that of isoprothiolane, which is widely used for rice disease control. Structure-activity relationship study indicated the the cis configuration and hydroxyl group in combretastatin A-4 are crucial to the antifungal effect. Molecular modeling indicated the binding sites of combretastatin A-4 and carbendazim on fungal tubulin are totally different. The bioactivity of combretastatin A-4 and its derivatives against carbendazim-resistant strains was demonstrated in this study. The results provide a new approach for fungicide discovery and fungicide resistance management.
Synthesis, crystal structure and cytotoxic properties of nitrocombretastatins (E)- and (Z)-5-(4-methoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene
Gerova, Mariana S.,Encheva, Gergina R.,Nikolova, Rositsa P.,Chanev, Christo D.,Shivachev, Boris L.,Apostolova, Margarita D.,Petrov, Ognyan I.
, p. 105 - 112 (2016/02/09)
(Z)-5-(4-Methoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene (2) is the key intermediate for the preparation of several anticancer agents, belonging to the group of aminocombretastatins (AC7739, AVE8062). Synthesis of the title compounds was achieved by a modified Wittig reaction under Boden's conditions using potassium carbonate as a base and 18-crown-6 as a phase transfer catalyst. Both π-diastereoisomers were characterized by single crystal X-ray diffraction analysis, 1H and 13C NMR spectroscopy. (E)-5-(4-Methoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene (1) crystallizes in the orthorhombic space group Pbca (N° 61) with one molecule per asymmetric unit while (Z)-5-(4-methoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene (2) crystallizes in the monoclinic space group P21/c (N° 14) also with one molecule per asymmetric unit. In both compounds no typical hydrogen bonding interactions could be located. The three-dimensional crystal structure is stabilized by C-H···O interactions. The cytotoxicity of synthesized nitrocombretastatins was also evaluated. The Z-stilbene 2 inhibited cell growth with IC50 of 0.15 and 0.11 μM following 72 h treatment in EA.hy926 and MG-63 cell lines.
Design and Synthesis of Aminostilbene-Arylpropenones as Tubulin Polymerization Inhibitors
Kamal, Ahmed,Kumar, G. Bharath,Polepalli, Sowjanya,Shaik, Anver Basha,Reddy, Vangala Santhosh,Reddy, M. Kashi,Reddy, Ch. Ratna,Mahesh, Rasala,Kapure, Jeevak Sopanrao,Jain, Nishant
, p. 2565 - 2579 (2015/08/24)
A series of aminostilbene - arylpropenones were designed and synthesized by Michael addition and were investigated for their cytotoxic activity against various human cancer cell lines. Some of the investigated compounds exhibited significant antiproliferative activity against a panel of 60 human cancer cell lines of the US National Cancer Institute, with 50% growth inhibition (GI50) values in the range from 50 value of 50) values ranging from 0.011 to 8.56μM. A cell cycle assay revealed that these compounds arrested the G2/M phase of the cell cycle. Two compounds exhibited strong inhibitory effects on tubulin assembly with IC50 values of 0.71 and 0.79μM. Moreover, dot-blot analysis of cyclinB1 demonstrated that some of the congeners strongly induced cyclinB1 protein levels. Molecular docking studies indicated that these compounds occupy the colchicine binding site of tubulin.
Synthesis and biological evaluation of 1,2,3-triazole linked aminocombretastatin conjugates as mitochondrial mediated apoptosis inducers
Kamal, Ahmed,Shaik, Bajee,Nayak, V. Lakshma,Nagaraju, Burri,Kapure, Jeevak Sopanrao,Shaheer Malik,Shaik, Thokhir Basha,Prasad
, p. 5155 - 5167 (2014/12/11)
A series of 1,2,3-triazole linked aminocombretastatin conjugates were synthesized and evaluated for cytotoxicity, inhibition of tubulin polymerization and apoptosis inducing ability. Most of the conjugates exhibited significant anticancer activity against
METHOD FOR PREPARING COMBRETASTATIN
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Page/Page column 4-5, (2011/06/19)
The Invention relates to a method for preparing a combretastatin (A): formula (I) in the form of a base or of an addition salt with an acid, which comprises coupling, in the presence of a base and of T3P, the salt of the (Z)-amino compound of formula (II)
Synthesis and biological evaluation of combretastatin analogs as cell cycle inhibitors of the G1 to S transition in Saccharomyces cerevisiae
Coccetti, Paola,Montano, Giuseppe,Lombardo, Alessandro,Tripodi, Farida,Orsini, Fulvia,Pagliarin, Roberto
supporting information; experimental part, p. 2780 - 2784 (2010/08/19)
A series of Z and E combretastatin A-4 analogs bearing different substituents (OH, F, NO2, NH2, B(OH)2) in the 3′ position were synthesized. These derivatives and Z and E combretastatin A-1 were analysed by monitoring their ability to inhibit cell growth in Saccharomyces cerevisiae. Combretastatin A-1 (2a), A-4 (2b) and compound 2c were found to inhibit yeast growth. Moreover, combretatstatin A-4 (2b) and compound 2c induced a G1 arrest by affecting the synthesis of Clb5 protein, the principal S-phase cyclin. The G1 arrest is coincident with the activation of the stress activated kinase Snf1.
Synthesis of conjugates of amino-combretastatin with tuftsin derivatives as potential anticancer agents
Dzierzbicka
scheme or table, p. 81 - 85 (2009/08/08)
Novel 3′-N-(tuftsin or retro-tuftsin)-amino-combretastatin conjugates have been synthesized as potential anticancer compounds. We hope that the conjugation of immunomodulators like tuftsin derivatives with amino-combretastatin A-4 would improve the therap
Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents
Monk, Keith A.,Siles, Rogelio,Hadimani, Mallinath B.,Mugabe, Benon E.,Ackley, J. Freeland,Studerus, Scott W.,Edvardsen, Klaus,Trawick, Mary Lynn,Garner, Charles M.,Rhodes, Monte R.,Pettit, George R.,Pinney, Kevin G.
, p. 3231 - 3244 (2007/10/03)
A series of analogs with nitro or serinamide substituents at the C-2′-, C-5′-, or C-6′-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in
