Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides

Yogesh Yadav; Deepti Sharma; Kumar Kaushik; Vineet Kumar; Amitabh Jha; Ashok K Prasad; Christophe Len; Sanjay V Malhotra; Jesper Wengel; Virinder S Parmar

doi:10.3390/molecules24213922

Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides

Molecules. 2019 Oct 30;24(21):3922. doi: 10.3390/molecules24213922.

Authors

Yogesh Yadav^{1

2

3}, Deepti Sharma^{4

5}, Kumar Kaushik⁶, Vineet Kumar^{7

8

9}, Amitabh Jha¹⁰, Ashok K Prasad¹¹, Christophe Len¹², Sanjay V Malhotra^{13

14}, Jesper Wengel¹⁵, Virinder S Parmar^{16

17

18}

Affiliations

¹ Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India. yogeshyadav77@gmail.com.
² Medicinal Chemistry Laboratory, Department of Chemistry, Acadia University, Wolfville, NS B4P 2R6, Canada. yogeshyadav77@gmail.com.
³ SUN Pharmaceuticals R&D, Gurgaon, Sarhaul, Sector-18, Haryana-122 015, India. yogeshyadav77@gmail.com.
⁴ Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India. deeptichem@rediffmail.com.
⁵ Sri Venkateswara College, Benito Juarez Road, Dhaula Kuan, University of Delhi, Delhi 110 021, India. deeptichem@rediffmail.com.
⁶ Department of Chemistry and Environmental Science, Medgar Evers College, The City University of New York, 1638 Bedford Avenue, Brooklyn, NY 11225, USA. kumar.kaushik.drdo@gmail.com.
⁷ Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India. iamvineet@gmail.com.
⁸ Laboratory of Synthetic Chemistry, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 2170, USA. iamvineet@gmail.com.
⁹ Department of Radiation Oncology, Stanford University, 1050A Arastradero Road, A252, Palo Alto, CA 94304, USA. iamvineet@gmail.com.
¹⁰ Medicinal Chemistry Laboratory, Department of Chemistry, Acadia University, Wolfville, NS B4P 2R6, Canada. amitabh.jha@acadiau.ca.
¹¹ Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India. ashokenzyme@gmail.com.
¹² Chimie ParisTech, PSL University, CNRS Institute of Chemistry for Life and Health Sciences-i-CLeHS, 11 rue Pierre et Marie Curie, F-75005 Paris, France. christophe.len@chimieparistech.psl.eu.
¹³ Laboratory of Synthetic Chemistry, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 2170, USA. smalhotra@stanford.edu.
¹⁴ Department of Radiation Oncology, Stanford University, 1050A Arastradero Road, A252, Palo Alto, CA 94304, USA. smalhotra@stanford.edu.
¹⁵ Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark. jwe@sdu.dk.
¹⁶ Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India. vparmar@mec.cuny.edu.
¹⁷ Department of Chemistry and Environmental Science, Medgar Evers College, The City University of New York, 1638 Bedford Avenue, Brooklyn, NY 11225, USA. vparmar@mec.cuny.edu.
¹⁸ Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark. vparmar@mec.cuny.edu.

Abstract

The synthesis of novel pyrazolylnucleosides 3a-e, 4a-e, 5a-e, and 6a-e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a-e and 6a-e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI₅₀ 9.3 µM) and breast cancer cell line HS 578T (GI₅₀ 3.0 µM).

Keywords: NCI-60; NOESY study; anticancer; modified nucleosides; pyrazolylnucleosides.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Carbon-13 Magnetic Resonance Spectroscopy
Nucleosides / chemical synthesis*
Nucleosides / chemistry
Nucleosides / pharmacology*
Proton Magnetic Resonance Spectroscopy
Pyrazines / chemical synthesis*
Pyrazines / chemistry
Pyrazines / pharmacology*
Stereoisomerism
Toxicity Tests

Substances

Antineoplastic Agents
Nucleosides
Pyrazines