Development of a novel nitro-derivative of noscapine for the potential treatment of drug-resistant ovarian cancer and T-cell lymphoma

Molecular Pharmacology
Ritu AnejaHarish C Joshi

Abstract

We have shown previously that an antitussive plant alkaloid, noscapine, binds tubulin, displays anticancer activity, and has a safe pharmacological profile in humans. Structure-function analyses pointed to a proton at position-9 of the isoquinoline ring that can be modified without compromising tubulin binding activity. Thus, many noscapine analogs with different functional moieties at position-9 were synthesized. Those analogs that kill human cancer cells resistant to other antimicrotubule agents, vincas and taxanes, were screened. Here, we present one such analog, 9-nitro-noscapine (9-nitro-nos), which binds tubulin and induces apoptosis selectively in tumor cells (ovarian and T-cell lymphoma) resistant to paclitaxel, vinblastine, and teniposide. 9-Nitro-nos treatment at doses as high as 100 microM did not affect the cell cycle profile of normal human fibroblasts. This selectivity of 9-nitro-nos for cancer cells represents a unique edge over the other available antimitotics. 9-Nitro-nos perturbs the progression of cell cycle by mitotic arrest, followed by apoptotic cell death associated with increased caspase-3 activation and appearance of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. Thus, we c...Continue Reading

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Citations

Jul 15, 2009·Cancer Chemotherapy and Pharmacology·Jitender MadanAnju Katyal
May 6, 2011·Journal of Computer-aided Molecular Design·Pradeep K NaikHarish C Joshi
Dec 16, 2011·Journal of Computer-aided Molecular Design·Pradeep K NaikHarish C Joshi
Jun 27, 2012·Pharmaceutical Research·Melissa M GajewskiJack A Tuszynski
Jul 23, 2014·European Journal of Medicinal Chemistry·Elena PorcùGiampietro Viola
Mar 23, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ritu AnejaHarish C Joshi
Jul 26, 2011·Chemical Biology & Drug Design·Laleh Alisaraie, Jack A Tuszynski
Mar 8, 2011·Medicinal Research Reviews·Richard A StantonRitu Aneja
Apr 19, 2015·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Monireh AfzaliSeyed Nasser Ostad
Sep 23, 2014·European Journal of Medicinal Chemistry·Ramandeep KaurJitender Bariwal
Nov 20, 2010·Biochemical Pharmacology·Vaishali PannuRitu Aneja
Jan 15, 2015·Phytochemistry·Xue ChenPeter J Facchini
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Sep 30, 2006·Bioorganic & Medicinal Chemistry·Ritu AnejaHarish C Joshi
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Dec 8, 2014·Journal of Computer-aided Molecular Design·Seneha SantoshiPradeep Kumar Naik
Sep 14, 2019·Biotechnology Reports·Luke RichardsSally L Gras

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