Synthesis and investigation of new Hesperadin analogues antitumor effects on HeLa cells

Shamsipour, Fereshteh; Hosseinzadeh, Saeeideh; Arab, Seyed Shahriar; Vafaei, Sedigheh; Farid, Samira; Jeddi-Tehrani, Mahmood; Balalaie, Saeed

doi:10.1007/s12154-014-0111-3

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…Hesperadin is an indolinone inhibitor of Aurora B [64, 65]. Its sulphonamide group extends beyond the ATP-pocket and into the adjacent hydrophobic pocket [66].…”

Section: Resultsmentioning

confidence: 99%

Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny

Berry¹,

Chen²,

Francia³

et al. 2018

Cell. Mol. Life Sci.

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The phylum Apicomplexa encompasses deadly pathogens such as malaria and Cryptosporidium. Apicomplexa cell division is mechanistically divergent from that of their mammalian host, potentially representing an attractive source of drug targets. Depending on the species, apicomplexan parasites can modulate the output of cell division, producing two to thousands of daughter cells at once. The inherent flexibility of their cell division mechanisms allows these parasites to adapt to different niches, facilitating their dissemination. Toxoplasma gondii tachyzoites divide using a unique form of cell division called endodyogeny. This process involves a single round of DNA replication, closed nuclear mitosis, and assembly of two daughter cells within a mother. In higher Eukaryotes, the four-subunit chromosomal passenger complex (CPC) (Aurora kinase B (ARKB)/INCENP/Borealin/Survivin) promotes chromosome bi-orientation by detaching incorrect kinetochore-microtubule attachments, playing an essential role in controlling cell division fidelity. Herein, we report the characterization of the Toxoplasma CPC (Aurora kinase 1 (Ark1)/INCENP1/INCENP2). We show that the CPC exhibits dynamic localization in a cell cycle-dependent manner. TgArk1 interacts with both TgINCENPs, with TgINCENP2 being essential for its translocation to the nucleus. While TgINCENP1 appears to be dispensable, interfering with TgArk1 or TgINCENP2 results in pronounced division and growth defects. Significant anti-cancer drug development efforts have focused on targeting human ARKB. Parasite treatment with low doses of hesperadin, a known inhibitor of human ARKB at higher concentrations, phenocopies the TgArk1 and TgINCENP2 mutants. Overall, our study provides new insights into the mechanisms underpinning cell cycle control in Apicomplexa, and highlights TgArk1 as potential drug target.

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“…Hesperadin is an indolinone inhibitor of Aurora B [64, 65]. Its sulphonamide group extends beyond the ATP-pocket and into the adjacent hydrophobic pocket [66].…”

Section: Resultsmentioning

confidence: 99%

Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny

Berry¹,

Chen²,

Francia³

et al. 2018

Cell. Mol. Life Sci.

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“…The forces of interaction between the two molecules are through hydrogen bonding and van-der Waals contact [ 64 ]. Further research on hesperadin analogues has revealed that additional hydrogen bonding by lipophilic substitution in the indolinone core could confer enhanced stability and activity to the drug [ 65 ]. It has been previously shown that hesperadin causes abnormal mitosis and impairment in cytokinesis.…”

Section: Targeting Aurkb In Cancermentioning

confidence: 99%

“…It has been previously shown that hesperadin causes abnormal mitosis and impairment in cytokinesis. HeLa cells treated with hesperidin do not proliferate and become polyploid in nature [ 65 ].…”

Section: Targeting Aurkb In Cancermentioning

confidence: 99%

Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

Borah

Reddy

2021

Molecules

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Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression. Deregulation of AURKB is observed in several tumors and its overexpression is frequently linked to tumor cell invasion, metastasis and drug resistance. AURKB has emerged as an attractive drug target leading to the development of small molecule inhibitors. This review summarizes recent findings pertaining to the role of AURKB in tumor development, therapy related drug resistance, and its inhibition as a potential therapeutic strategy for cancer. We discuss AURKB inhibitors that are in preclinical and clinical development and combination studies of AURKB inhibition with other therapeutic strategies.

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Leishmania donovani Aurora kinase: A promising therapeutic target against visceral leishmaniasis

Chhajer

Bhattacharyya

Didwania

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

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Synthesis and investigation of new Hesperadin analogues antitumor effects on HeLa cells

Cited by 5 publications

References 20 publications

Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny

Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny

Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

Leishmania donovani Aurora kinase: A promising therapeutic target against visceral leishmaniasis

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