CC BY ND NC 4.0 · SynOpen 2018; 02(02): 0114-0121
DOI: 10.1055/s-0036-1591980
paper
Copyright with the author

Synthesis and Cytotoxic Evaluation of 3-(4-Fluorophenyl)-4,5-dihydro-5-(3,4,5-trimethoxy/4-nitrophenyl)-N-(substituted-phenyl)pyrazole-1-carboxamide Analogues

Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan 302 039, India   Email: jawedpharma@gmail.com
,
Bhawani S. Kumawat
Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan 302 039, India   Email: jawedpharma@gmail.com
,
Sonu Kumawat
Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan 302 039, India   Email: jawedpharma@gmail.com
,
Piush Sharma
Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan 302 039, India   Email: jawedpharma@gmail.com
,
Mohammad A. Bakht
Department of Chemistry, College of Science & Humanities, Prince Sattam Bin Abdulaziz University, P.O. Box 11323, Saudi Arabia
,
Mohd Z. Hassan
Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
,
Afzal Hussain
Department of Pharmaceutical Science & Technology, Birla Institute of Science & Technology, Mesra, Ranchi, Jharkhand 835 215, India
,
Pankaj Saraswat
Department of Pharmaceutical Chemistry, Alwar Pharmacy College, Alwar, Rajasthan 301 030, India
,
Habibullah Khalilullah
Department of Pharmaceutical Chemistry, Unaizah College of Pharmacy, Qassim University, Al-Qassim 51911, Kingdom of Saudi Arabia
› Author Affiliations
Further Information

Publication History

Received: 24 January 2018

Accepted after revision: 14 March 2018

Publication Date:
23 April 2018 (online)

Abstract

A novel series of 3-(4-fluorophenyl)-4,5-dihydro-5-(3,4,5-trimethoxy/4-nitro phenyl)-N-(substituted-phenyl)pyrazole-1-carboxamide analogues 4an was synthesized in two steps from 4-fluoroacetophenone. The pyrazoline analogues were evaluated for cytotoxicity against two breast cancer cell lines (MCF-7 and MBA-MD-231) by the sulforhodamine B (SRB) assay. N-(4-Chlorophenyl)-3-(4-fluorophenyl)-5-(4-nitrophenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide (4b) showed the most promising cytotoxicity among the series, with GI50 <0.1 and 45.8 μM against the cancer cell lines, MCF-7 and MDA-MB-231, respectively. The anticancer activity of 4b was found to be comparable to that of the standard drug adriamycin (GI50 <0.1) against the MCF-7 cancer cell line. Structure activity relationships (SAR) are also considered.

 
  • References

  • 1 Siegel RL. Miller KD. Jemal A. CA: Cancer J. Clin. 2017; 67: 7
  • 2 Nandakumar A. National Cancer Registry Programme. Indian Council for Medical Research, Consolidated Report of the Population Based Cancer Registries 1990-96. New Delhi: Indian Council of Medical Research. 2009;
  • 3 Cancer fact sheet February 2017: http://www.who.int/mediacentre/factsheets/fs297/en/
  • 4 Aydemir N. Bilaloglu R. Mutat. Res., Genet. Toxicol. Environ. Mutagen. 2003; 537: 43
  • 5 Dees EC. Rowinsky EK. Noe DA. O’Reilly S. Adjei AA. Elza-Brown K. Donehower RC. Invest. New Drugs 2003; 21: 75
  • 6 Berg SL. Blaney SM. Sullivan J. Bernstein M. Dubowy R. Harris MB. J. Pediatr. Hematol./Oncol. 2000; 22: 506
  • 7 Ramaswamy B. Mrozek E. Kuebler JP. Bekaii-Saab T. Kraut EH. Invest. New Drugs 2011; 29: 347
  • 8 Na JI. Na JY. Choi WY. Lee MC. Park MS. Choi KH. Lee JK. Kim KT. Park JT. Kim HS. Am. J. Transl. Res. 2015; 7: 751
  • 9 Chang LC. Lin HY. Tsai MT. Chou RH. Lee FY. Teng CM. Hsieh MT. Hung HY. Huang LJ. Yu YL. Kyo HC. Br. J. Pharmacol. 2014; 171: 4010
  • 10 George DJ. Clin. Cancer Res. 2007; 13: 753
  • 11 Rini B. Wilding G. Hudes G. Stadler WM. Kim S. Tarazi J. Bycott P. Liau K. Dutcher J. EJC Suppl. 2007; 5: 300
  • 12 Lv PC. Li DD. Li QS. Lu X. Xiao ZP. Zhu HL. Bioorg. Med. Chem. Lett. 2011; 21: 5374
  • 13 Havrylyuk D. Zimenkovsky B. Vasylenko O. Gzella A. Lesyk R. J. Med. Chem. 2012; 55: 8630
  • 14 Qin H. Shang Z. Jantan I. Tan OU. Hussain MA. Sher M. Bukhari SN. A. RSC Adv. 2015; 5: 463330
  • 15 Ahsan MJ. Samy GJ. Habibullah K. Bakht MA. Hassan MZ. Eur. J. Med. Chem. 2011; 46: 5694
  • 16 Ahsan MJ. Samy GJ. Khalilullah H. Moham G. Stables JP. Bioorg. Med. Chem. Lett. 2012; 22: 7029
  • 17 Shamsuzzaman, Khanam H. Dar AM. Siddiqui N. Rehman S. J. Saudi Chem. Soc. 2016; 20: 7
  • 18 Yang B. Yang YS. Yang N. Li G. Zhu HL. Sci. Rep. 2016; 6: 27571
  • 19 Elbayaa RY. Badr MH. Khalil AA. Abdelhadi M. Drug Res. (Stuttgart, Ger.) 2013; 63: 271
  • 20 Ahsan MJ. Samy GJ. Stables JP. Med. Chem. Res. 2013; 22: 2746
  • 21 Gul HI. Yamali C. Sakagami H. Angeli A. Leitans J. Kazaks A. Tars K. Ozgun DO. Supuran CT. Bioorg. Chem. 2018; 77: 411
  • 22 Yakaiah S. Kumar PS. V. Rani PB. Prasad KD. Aparna P. Bioorg. Med. Chem. Lett. 2018; 28: 630
  • 23 Ahsan MJ. Lett. Drug Des. Discovery 2012; 9: 823
  • 24 Vichai V. Kirtikara K. Nat. Protoc. 2006; 1: 1112