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.

4_1_49_52

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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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. 16 Jul. 2020
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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DOI Link: https://doi.org/10.5155/eurjchem.4.1.49-52.701

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