European Journal of Chemistry 2013, 4(1), 49-52 | doi: https://doi.org/10.5155/eurjchem.4.1.49-52.701 | Get rights and content

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Urease inhibition and anticancer activity of novel polyfunctional 5,6-dihydropyridine derivatives and their structure-activity relationship


Abdul Hameed (1,*) , Ayaz Anwar (2) , Khalid Mohammed Khan (3) , Rizwana Malik (4) , Fernaz Shahab (5) , Sadia Siddiq (6) , Fatima Zahra Basha (7) , Muhammad Iqbal Choudhary (8)

(1) Third World Labortary Building, International Center for Chemical and Biological Sciences, University Karachi, Karachi-75270, Pakistan
(2) Third World Labortary Building, International Center for Chemical and Biological Sciences, University Karachi, Karachi-75270, Pakistan
(3) Husein Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
(4) Husein Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
(5) Husein Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
(6) Husein Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
(7) Third World Labortary Building, International Center for Chemical and Biological Sciences, University Karachi, Karachi-75270, Pakistan
(8) Husein Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
(*) Corresponding Author

Received: 07 Nov 2012 | Revised: 04 Dec 2012 | Accepted: 27 Nov 2012 | Published: 31 Mar 2013 | Issue Date: March 2013

Abstract


A novel series of tricyano substituted polyfunctional 5,6-dihydropyridine 8a-n bearing functionalized aromatic rings at C-4 and C-6 position have been prepared from (α-methylbenzylidene) malononitriles in good to excellent yields (52-98%) in solvent free conditions. All the synthesized compounds (8a-n) were evaluated for their in vitro urease inhibition and anticancer activity against prostate cancer (PC3) and Hela cell lines. Compound 8k (4,6-bis(4-methoxyphenyl)-5,6-dihydropyridin) showed slightly better urease inhibitory potential (IC50 = 20.47 µM) as compared to standard thiourea (IC50 = 21 µM). Whilst in the case of anticancer studies the compound 8a 2-(4,6-bis(4-bromophenyl)-6-methyl-5,6-dihydropyridin found to be most active (IC50 = 4.40 and 8.80 µM) among the series when compared with standard doxorubicin 4 (IC50 = 0.91 and 3.1 µM) in both cell lines respectively. A structure-activity relationship of this series has been established on the basis of electronic effects and position of different substituents (H, Br, Cl, I, F, Me, OMe, OH, and NO2) present on the C-4 and C-6 phenyl rings. The anticancer activity evaluation of these pyridine derivatives envisage that the compound 8a could be putatively linked with doxorubicin IV to developed new anticancer prodrugs for multidrug resistant (MDR) cancer cells. All the synthesized compounds were characterized by spectroscopic techniques.

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Keywords


Hela cell line; Ureases Inhibition; Anticancer activity; Prostate cancer cell line; Knoevenagel condensation; Dihydropyridine derivatives

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DOI: 10.5155/eurjchem.4.1.49-52.701

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Funding information


Higher Education Commission (HEC), Pakistan; Husein Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi

Citations

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[1]. Jaiprakash N. Sangshetti, Deepak K. Lokwani, Rashmi S. Chouthe, Ashok Ganure, Bhuvan Raval, Firoz A. Kalam Khan, Devanand B. Shinde
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Medicinal Chemistry Research  23(11), 4893, 2014
DOI: 10.1007/s00044-014-1044-7
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[2]. Hong Pan, Man-Yi Han, Pinhua Li, Lei Wang
“On Water” Direct Catalytic Vinylogous Aldol Reaction of Silyl Glyoxylates
The Journal of Organic Chemistry  84(21), 14281, 2019
DOI: 10.1021/acs.joc.9b01945
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[3]. Estefanía Menéndez‐Pedregal, Ángel Manteca, Jesús Sánchez, J. Díez, M. Pilar Gamasa, Elena Lastra
Antimicrobial and Antitumor Activity of Enantiopure Pybox–Osmium Complexes
European Journal of Inorganic Chemistry  2015(8), 1424, 2015
DOI: 10.1002/ejic.201403173
/


[4]. Oleg V. Ershov, Ivan N. Bardasov
Synthesis of pyridine derivatives containing a tricyanobutadiene motif (microreview)
Chemistry of Heterocyclic Compounds  53(11), 1178, 2017
DOI: 10.1007/s10593-018-2190-5
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[5]. Arshia Arshia, Ajmal Khan, Khalid Mohammed Khan, Syed Muhammad Saad, Nida Iqbal Siddiqui, Sumaira Javaid, Shahnaz Perveen, M. Iqbal Choudhary
Synthesis and urease inhibitory activities of benzophenone semicarbazones/thiosemicarbazones
Medicinal Chemistry Research  25(11), 2666, 2016
DOI: 10.1007/s00044-016-1673-0
/


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A facile synthesis of new 5-aryl-thiophenes bearing sulfonamide moiety via Pd(0)-catalyzed Suzuki–Miyaura cross coupling reactions and 5-bromothiophene-2-acetamide: As potent urease inhibitor, antibacterial agent and hemolytically active compounds
Journal of Saudi Chemical Society  21, S403, 2017
DOI: 10.1016/j.jscs.2014.04.007
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[7]. Shahbaz Shamim, Khalid Mohammed Khan, Uzma Salar, Farman Ali, Muhammad Arif Lodhi, Muhammad Taha, Farman Ali Khan, Sajda Ashraf, Zaheer Ul-Haq, Muhammad Ali, Shahnaz Perveen
5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1 H )-ones: As potent urease inhibitors; synthesis, in vitro screening, and molecular modeling study
Bioorganic Chemistry  76, 37, 2018
DOI: 10.1016/j.bioorg.2017.10.021
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[8]. Mnaza Noreen, Nasir Rasool, Yasmeen Gull, Muhammad Zubair, Tariq Mahmood, Khurshid Ayub, Faiz-ul-Hassan Nasim, Asma Yaqoob, Muhammad Zia-Ul-Haq, Vincenzo de Feo
Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties
Molecules  20(11), 19914, 2015
DOI: 10.3390/molecules201119661
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[9]. Jalaluddin A. Khan, Atia-tul- Wahab, Sumaira Javaid, Maryam AL-Ghamdi, Etimad Huwait, Muniza Shaikh, Amsal Shafqat, M. Iqbal Choudhary
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Medicinal Chemistry Research  26(10), 2452, 2017
DOI: 10.1007/s00044-017-1945-3
/


[10]. Ayaz Anwar, Ruqaiyyah Siddiqui, Abdul Hameed, Muhammad R. Shah, Naveed A. Khan
Synthetic Dihydropyridines as Novel Antiacanthamoebic Agents
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DOI: 10.2174/1573406415666190722113412
/


References


[1]. Hargreaves, S. L.; Pilkington, B. L.; Russell, S. E.; Worthington, P. A. Tetrahedron Lett. 2000, 41, 1653-1656.
http://dx.doi.org/10.1016/S0040-4039(00)00007-1

[2]. Malicorne, G.; Bompart, J.; Giral, L.; Despaux, E. Eur. J. Med. Chem. 1991, 26, 3-11.
http://dx.doi.org/10.1016/0223-5234(91)90207-4

[3]. Szoko, E.; Tabi, T. J. Pharm, Biomed. Anal. 2010, 53, 1180-1192.

[4]. Hameed, A.; Anwar, A.; Yousaf, S.; Khan, K. M.; Basha, F. Z. Eur. J. Chem. 2012, 3, 179-185.
http://dx.doi.org/10.5155/eurjchem.3.2.179-185.562

[5]. Burne, R. A.; Chen, Y.-Y. M. Microbes and Infect. 2000, 2, 533-542.
http://dx.doi.org/10.1016/S1286-4579(00)00312-9

[6]. Mobley, H. L. T.; Hausinger, R. P. Microbiol. Rev. 1989, 53, 85-100.
PMid:2651866 PMCid:372718

[7]. Menna, P.; Gonzalez Paz, O.; Chello, M.; Covino, E.; Salvatorelli, E.; Minotti, G. Expet. Opin. Drug Saf. 2012, 11, S21-S36.
http://dx.doi.org/10.1517/14740338.2011.589834
PMid:21635149

[8]. Koch, T.; Barthel, B.; Kalet, B.; Rudnicki, D.; Post, G.; Burkhart, D.: Anthracycline-Formaldehyde Conjugates and Their Targeted Prodrugs Anthracycline Chemistry and Biology II. Krohn, K., Ed.; Springer Berlin/Heidelberg, 2008, 283, 141-170.

[9]. Talelli, M.; Morita, K.; Rijcken, C. J.; Aben, R. W.; Lammers, T.; Scheeren, H. W.; Van Nostrum, C. F.; Storm, G.; Hennink, W. E. Bioconjug. Chem. 2011, 22, 2519-2530.
http://dx.doi.org/10.1021/bc2003499
PMid:22017211

[10]. Volm, M.; Mattern, J.; Samsel, B. Br. J. Cancer 1991, 64, 700-704.
http://dx.doi.org/10.1038/bjc.1991.384
PMid:1680367 PMCid:1977695

[11]. Toyota, K.; Shinkai, H.; Eto, H.; Kamimura, A.; Eguchi, C.; Ohsumi, K.; Tsuruo, T. U.S. Patent Application 5216172, 1993. 01.07.

[12]. Abadi, A. H.; Ibrahim, T. M.; Abouzid, K. M.; Lehmann, J.; Tinsley, H. N.; Gary, B. D.; Piazza, G. A. Bioorg. Med. Chem. 2009, 17, 5974-5982.
http://dx.doi.org/10.1016/j.bmc.2009.06.063
PMid:19628397

[13]. Weatherburn, M. W. Anal. Chem. 1967, 39, 971-974.
http://dx.doi.org/10.1021/ac60252a045

[14]. Mosmann, T. J. Immunol. Methods 1983, 65, 55-63.


How to cite


Hameed, A.; Anwar, A.; Khan, K.; Malik, R.; Shahab, F.; Siddiq, S.; Basha, F.; Choudhary, M. Eur. J. Chem. 2013, 4(1), 49-52. doi:10.5155/eurjchem.4.1.49-52.701
Hameed, A.; Anwar, A.; Khan, K.; Malik, R.; Shahab, F.; Siddiq, S.; Basha, F.; Choudhary, M. Urease inhibition and anticancer activity of novel polyfunctional 5,6-dihydropyridine derivatives and their structure-activity relationship. Eur. J. Chem. 2013, 4(1), 49-52. doi:10.5155/eurjchem.4.1.49-52.701
Hameed, A., Anwar, A., Khan, K., Malik, R., Shahab, F., Siddiq, S., Basha, F., & Choudhary, M. (2013). Urease inhibition and anticancer activity of novel polyfunctional 5,6-dihydropyridine derivatives and their structure-activity relationship. European Journal of Chemistry, 4(1), 49-52. doi:10.5155/eurjchem.4.1.49-52.701
Hameed, Abdul, Ayaz Anwar, Khalid Mohammed Khan, Rizwana Malik, Fernaz Shahab, Sadia Siddiq, Fatima Zahra Basha, & Muhammad Iqbal Choudhary. "Urease inhibition and anticancer activity of novel polyfunctional 5,6-dihydropyridine derivatives and their structure-activity relationship." European Journal of Chemistry [Online], 4.1 (2013): 49-52. Web. 28 May. 2023
Hameed, Abdul, Anwar, Ayaz, Khan, Khalid, Malik, Rizwana, Shahab, Fernaz, Siddiq, Sadia, Basha, Fatima, AND Choudhary, Muhammad. "Urease inhibition and anticancer activity of novel polyfunctional 5,6-dihydropyridine derivatives and their structure-activity relationship" European Journal of Chemistry [Online], Volume 4 Number 1 (31 March 2013)

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