A Small Molecule with Bridged Carbonyl and Tri-fluoro-aceto-phenone Groups Impedes Microtubule Dynamics and Subsequently Triggers Cancer Cell Apoptosis.
Acetophenones
/ chemistry
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Benzothiazoles
/ chemistry
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Density Functional Theory
Drug Screening Assays, Antitumor
Humans
MCF-7 Cells
Microtubules
/ drug effects
Molecular Structure
Polymerization
/ drug effects
Small Molecule Libraries
/ chemistry
Tubulin
/ metabolism
Tumor Cells, Cultured
Microtubule targeting agent
anti-cancer
apoptosis
bim
p53
puma
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
06 09 2021
06 09 2021
Historique:
revised:
13
05
2021
received:
19
03
2021
pubmed:
14
5
2021
medline:
26
2
2022
entrez:
13
5
2021
Statut:
ppublish
Résumé
We identified a new microtubule targeted small molecule, which showed significant anticancer activity and induced apoptotic death of cancer cells. Precisely the central bridged carbonyl group and trifluoro-acetophenone group of a bis-benzothiazole molecule (BBT) interacts with tubulin close to the curcumin site and perturbs microtubule dynamics as well as causes microtubule depolymerization. We observed a significant enhancement of fluorescence while BBT interacts with the tubulin through bridged carbonyl moiety, a similar phenomenon to colchicine. Further, BBT activates tumor-suppressing bim and p53-puma axes to inhibit cancer survival. It also shows promising results against a tumor spheroid model. BBT is also capable of tumor regression, which shows that this molecule can serve as a potential template for the design of next-generation microtubule targeted anticancer drugs.
Identifiants
pubmed: 33983670
doi: 10.1002/cmdc.202100192
doi:
Substances chimiques
Acetophenones
0
Antineoplastic Agents
0
Benzothiazoles
0
Small Molecule Libraries
0
Tubulin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2703-2714Subventions
Organisme : SERB, India
ID : CRG/2019/000670
Organisme : SERB-STAR
ID : STR/2020/000048
Informations de copyright
© 2021 Wiley-VCH GmbH.
Références
E. Mandelkow, E.-M. Mandelkow, Curr. Opin. Struct. Biol. 1994, 4, 171-179.
J. Löwe, H. Li, K. H. Downing, E. Nogales, J. Mol. Biol. 2001, 313, 1045-1057.
K. H. Downing, E. Nogales, Curr. Opin. Struct. Biol. 1998, 8, 785-791.
R. H. Wade, A. A. Hyman, Curr. Opin. Cell Biol. 1997, 9, 12-17.
M. A. Lampson, T. M. Kapoor, Nat. Chem. Biol. 2006, 2, 19-27.
E. Komlodi-Pasztor, D. Sackett, J. Wilkerson, T. Fojo, Nat. Rev. Clin. Oncol. 2011, 8, 244-250.
J. J. Field, A. Kanakkanthara, J. H. Miller, Bioorg. Med. Chem. 2014, 22, 5050-5059.
A. Ganguly, H. Yang, R. Sharma, K. D. Patel, F. Cabral, J. Biol. Chem. 2012, 287, 43359-43369.
M. Karbowski, J. H. Spodnik, M. Teranishi, M. Wozniak, Y. Nishizawa, J. Usukura, T. Wakabayashi, J. Cell Sci. 2001, 114, 281-291.
A. Akhmanova, M. O. Steinmetz, Nat. Rev. Mol. Cell Biol. 2015, 16, 711-726.
S. Chakraborti, L. Das, N. Kapoor, A. Das, V. Dwivedi, A. Poddar, G. Chakraborti, M. Janik, G. Basu, D. Panda, P. Chakrabarti, A. Surolia, B. Bhattacharyya, J. Med. Chem. 2011, 54, 6183-6196.
D. Li, M. B. Sewer, Endocrinology 2010, 151, 4313-4323.
D. Chen, Q. Zhou, Proc. Natl. Acad. Sci. USA 2004, 101, 1235-1240.
H. Puthalakath, D. C. Huang, L. A. O′Reilly, S. M. King, A. Strasser, Mol. Cell 1999, 3, 287-296.
T. T. Tan, K. Degenhardt, D. A. Nelson, B. Beaudoin, W. Nieves-Neira, P. Bouillet, A. Villunger, J. M. Adams, E. White, Cancer Cell 2005, 7, 227-238.
A. Sunters, S. Fernández de Mattos, M. Stahl, J. J. Brosens, G. Zoumpoulidou, C. A. Saunders, P. J. Coffer, R. H. Medema, R. C. Coombes, E. W. Lam, J. Biol. Chem. 2003, 278, 49795-49805.
P. Bouillet, D. Metcalf, D. C. Huang, D. M. Tarlinton, T. W. Kay, F. Köntgen, J. M. Adams, A. Strasser, Science 1999, 286, 1735-1738.
D. Chen, M. Wang, S. Zhou, Q. Zhou, EMBO J 2002, 21, 6801-6810.
N. R. Khawaja, M. Carré, H. Kovacic, M. A. Estève, D. Braguer, Mol. Pharmacol. 2008, 74, 1072-1083.
T. Tong, J. Ji, S. Jin, X. Li, W. Fan, Y. Song, M. Wang, Z. Liu, M. Wu, Q. Zhan, Mol. Cell. Biol. 2005, 25, 4488-4500.
B. Pourroy, M. Carré, S. Honoré, V. Bourgarel-Rey, A. Kruczynski, C. Briand, D. Braguer, Mol. Pharmacol. 2004, 66, 580-591.
H. Yamaguchi, J. Chen, K. Bhalla, H. G. Wang, J. Biol. Chem. 2004, 279, 39431-39437.
C. Bressin, V. Bourgarel-Rey, M. Carré, B. Pourroy, D. Arango, D. Braguer, Y. Barra, Anti-Cancer Drugs 2006, 17, 181-187.
P. Giannakakou, D. L. Sackett, Y. Ward, K. R. Webster, M. V. Blagosklonny, T. Fojo, Nat. Cell Biol. 2000, 2, 709-717.
X. M. Liu, J. D. Jiang, A. C. Ferrari, D. R. Budman, L. G. Wang, Br. J. Cancer 2003, 89, 1566-1573.
K. Rathinasamy, B. Jindal, J. Asthana, P. Singh, P. V. Balaji, D. Panda, BMC Cancer 2010, 10, 213.
R. B. Tishler, D. M. Lamppu, S. Park, B. D. Price, Cancer Res. 1995, 55, 6021-6025.
H. H. Wang, H. L. Li, R. Liu, Y. Zhang, K. Liao, Q. Wang, J. Z. Wang, S. J. Liu, JAD 2010, 21, 167-179.
S. Bates, K. H. Vousden, Cell. Mol. Life Sci. 1999, 55, 28-37.
M. H. Brodsky, W. Nordstrom, G. Tsang, E. Kwan, G. M. Rubin, J. M. Abrams, Cell 2000, 101, 103-113.
S. Jin, S. Martinek, W. S. Joo, J. R. Wortman, N. Mirkovic, A. Sali, M. D. Yandell, N. P. Pavletich, M. W. Young, A. J. Levine, Proc. Natl. Acad. Sci. USA 2000, 97, 7301-7306.
M. Ollmann, L. M. Young, C. J. Di Como, F. Karim, M. Belvin, S. Robertson, K. Whittaker, M. Demsky, W. W. Fisher, A. Buchman, G. Duyk, L. Friedman, C. Prives, C. Kopczynski, Cell 2000, 101, 91-101.
S. W. Lowe, A. W. Lin, Carcinogenesis 2000, 21, 485-495;
H. Ito, T. Kanzawa, S. Kondo, Y. Kondo, International journal of oncology 2005, 26, 589-596.
A. Rivkin, F. Yoshimura, A. E. Gabarda, Y. S. Cho, T. C. Chou, H. Dong, S. J. Danishefsky, J. Am. Chem. Soc. 2004, 126, 10913-10922.
A. Kamal, A. Mallareddy, M. Janaki Ramaiah, S. N. Pushpavalli, P. Suresh, C. Kishor, J. N. Murty, N. S. Rao, S. Ghosh, A. Addlagatta, M. Pal-Bhadra, Eur. J. Med. Chem. 2012, 56, 166-178.
Y. Ie, M. Nitani, M. Karakawa, H. Tada, Y. Aso, Adv. Funct. Mater. 2010, 20, 907.
J. Zhou, D. Panda, J. W. Landen, L. Wilson, H. C. Joshi, J. Biol. Chem. 2002, 277, 17200-17208.
J. P. Snyder, J. H. Nettles, B. Cornett, K. H. Downing, E. Nogales, Proc. Natl. Acad. Sci. USA 2001, 98, 5312-5316.
B. Bhattacharyya, J. Wolff, Proc. Natl. Acad. Sci. USA 1974, 71, 2627-2631.
K. K. Gupta, S. S. Bharne, K. Rathinasamy, N. R. Naik, D. Panda, FEBS J 2006, 273, 5320-5332.
A. A. Sablina, P. M. Chumakov, A. J. Levine, B. P. Kopnin, Oncogene 2001, 20, 899-909.
H. Yang, Y. Xie, D. Yang, D. Ren, Oncotarget 2017, 8, 25310-25322.
H. Okada, T. W. Mak, Nat. Rev. Cancer 2004, 4, 592-603.
L. M. Mu, R. J. Ju, R. Liu, Y. Z. Bu, J. Y. Zhang, X. Q. Li, F. Zeng, W. L. Lu, Adv. Drug Delivery Rev. 2017, 115, 46-56.
S. Mohapatra, A. Saha, P. Mondal, B. Jana, S. Ghosh, A. Biswas, S. Ghosh, Adv. Healthcare Mater. 2017, 6, 1600718.
D. Bhunia, A. Saha, A. Adak, G. Das, S. Ghosh, RSC Adv. 2016, 6, 113487.
M. Dean, T. Fojo, S. Bates, Nat. Rev. Cancer 2005, 5, 275-284.
S. Mohapatra, S. Nandi, R. Chowdhury, G. Das, S. Ghosh, K. Bhattacharyya, Phys. Chem. Chem. Phys. 2016, 18, 18381-18390.
D. Bhunia, S. Mohapatra, P. Kurkute, S. Ghosh, B. Jana, P. Mondal, A. Saha, G. Das, S. Ghosh, Chem. Commun. (Camb.) 2016, 52, 12657-12660.
A. Saha, S. Mohapatra, G. Das, B. Jana, S. Ghosh, D. Bhunia, S. Ghosh, ACS Appl. Mater. Interfaces 2017, 9, 176-188.