Synthesis and Evaluation of New Series of 1,4-Dihydropyridine Derivatives as Anticancer Agents

Anil Kumar Garige, Achaiah Garlapati


1,4-dihydropyridine derivatives represent one of the important classes of compounds possessing a wide variety of biological activities including anticancer activity. In the present study, (4-Alkyl/Aryl-1-substituted 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxilicacid, 3,5-bis [2(aminothioxomethyl)hydrazides]) (6 a-l) were synthesized by the reaction of 4-alkyl/aryl-3,5-dicarboalkoxy-2,6-dimethyl-1,4-dihydropyridines (4 a-l) with thisemicarbazide and evaluated for their anti-cancer properties.

All the synthesized compounds were characterized by IR, NMR and Mass spectra and were screened to evaluating for anticancer activity against three cell lines (MCF-7, HeLa and Hep G2) by using MTT assay method. The results showed that compounds 6j and 6l showed significant cytotoxicity with IC50 values ranging from 56µM - 74µM.



Cancer; 1,4-Dihydropyridines; MTT assay; Thiosemicarbazide.


A. Radadiya, V. Khedkar, A. Bavishi, H. Vala, S. Thakrar, D. Bhavsar, A. Shah and E. Coutinho, "Synthesis and 3D-QSAR study of 1,4-dihydropyridine derivatives as MDR cancer reverters", European Journal of Medicinal Chemistry, vol. 74, pp. 375- 387, 2014.

A. Hunter, E. LaCasse and R. Korneluk, "The inhibitors of apoptosis (IAPs) as cancer targets", Apoptosis, vol. 12, no. 9, pp. 1543-1568, 2007.

F. Shekari, H. Sadeghpour, K. Javidnia, L Saso, F. Nazari, O. Firuzi, R. Miri, "Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells", European Journal of Pharmacology, vol. 746 pp. 233–244, 2015.

F. Hadizadeh, Z. F. Hassanabad, M. Bamshad, H. Poorsoghat and M. F. Hassanabad, "Synthesis and antihypertensive activity of new 1,4-dihydrppyridines", Indian Journal of Chemistry, vol. 44B, pp. 2343-2347, 2005.

M. Jorjani, H. Rastegar, F. Roshanzamir, M. Varmazyari, M. Abdollahi, and A. Zarghi, "Synthesis and Biological Evaluation of New 1, 4-Dihydropyridines asAntihypertensives Agents in Rats", Iranian Journal of Pharmaceutical Research, vol. 2, pp 43-46, 2003.

A. Vijesh, A. Isloor, S. Peethambar, K. Shivananda, T. Arulmoli and N. Isloor, "Hantzsch reaction: Synthesis and characterization of some new 1,4-dihydropyridine derivatives as potent antimicrobial and antioxidant agents", European Journal of Medicinal Chemistry, vol. 46, no. 11, pp. 5591-5597, 2011.

H. Abu-Melha, "Synthesis, antibacterial and antifungal evaluation of novel 1,4-dihydropyridine derivatives", Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 113, pp. 115-122, 2013.

A. Fassihi, Z. Azadpour, N. Delbari, L. Saghaie, H. Memarian, R. Sabet, A. Alborzi, R. Miri, B. Pourabbas and J. Mardaneh, "Synthesis and antitubercular activity of novel 4-substituted imidazolyl-2,6-dimethyl-N3,N5-bisaryl-1,4-dihydropyridine-3,5-dicarboxamides", European Journal of Medicinal Chemistry, vol. 44, no. 8, pp. 3253-3258, 2009.

M. Khoshneviszadeh, N. Edraki, K. Javidnia, A. Alborzi, B. Pourabbas, J. Mardaneh and R. Miri, "Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents", Bioorganic & Medicinal Chemistry, vol. 17, no. 4, pp. 1579-1586, 2009.

V. Pandey, S. Bisht, M. Mishra, A. Kumar, M. Siddiqi, A. Verma, M. Mittal, S. Sane, S. Gupta and R. Tripathi, "Synthesis and molecular docking studies of 1-phenyl-4-glycosyl-dihydropyridines as potent antileishmanial agents", European Journal of Medicinal Chemistry, vol. 45, no. 6, pp. 2381-2388, 2010.

J. Reimão, M. Scotti and A. Tempone, "Anti-leishmanial and anti-trypanosomal activities of 1,4-dihydropyridines: In vitro evaluation and structure–activity relationship study", Bioorganic & Medicinal Chemistry, vol. 18, no. 22, pp. 8044-8053, 2010.

A. Kumar, R. Maurya, S. Sharma, M. Kumar and G. Bhatia, "Synthesis and biological evaluation of N-aryl-1,4-dihydropyridines as novel antidyslipidemic and antioxidant agents", European Journal of Medicinal Chemistry, vol. 45, no. 2, pp. 501-509, 2010.

K. Elumalai, M. Elumalai, K. Eluri, S. Srinivasan, M. Ashraf Ali, B. Venkateswara Reddy and S. Sarangi, "Facile synthesis, spectral characterization, antimicrobial and in vitro cytotoxicity of novel N3,N5-diisonicotinyl-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbohydrazide derivatives", Bulletin of Faculty of Pharmacy, Cairo University, vol. 54, no. 1, pp. 77-86, 2016.

R. Miri, K. Javidnia, Z. Amirghofran, S. Salimi, Z. Sabetghadam, S. Meili and A. Mehdipour, "Cytotoxic Effect of Some 1, 4-Dihydropyridine Derivatives Containing Nitroimidazole Moiety", Iranian Journal of Pharmaceutical Research, vol. 10, no. 3, pp. 497-503, 2011.

S. Amgoth, M. Porika, S. Abbagani, A. Garlapati and M. Vanga, "Synthesis, anticancer and MRP1 inhibitory activities of 4-alkyl/aryl-3,5-bis(carboethoxy/carbomethoxy)-1,4-dihydro-2,6-dimethylpyridines", Medicinal Chemistry Research, vol. 22, no. 1, pp. 147-155, 2012.

K. Sirisha, M. Shekhar, K. Umasankar, P. Mahendar, A. Sadanandam, G. Achaiah and V. Reddy, "Molecular docking studies and in vitro screening of new dihydropyridine derivatives as human MRP1 inhibitors", Bioorganic & Medicinal Chemistry, vol. 19, no. 10, pp. 3249-3254, 2011.

K. Sirisha, D. Bikshapathi, G. Achaiah and V. Reddy, "Synthesis, antibacterial and antimycobacterial activities of some new 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(aryl)-carbamoyl-1,4-dihydropyridines", European Journal of Medicinal Chemistry, vol. 46, no. 5, pp. 1564-1571, 2011.

K. Sirisha, G. Achaiah and V. Reddy, "Facile Synthesis and Antibacterial, Antitubercular, and Anticancer Activities of Novel 1,4-Dihydropyridines", Archiv der Pharmazie, vol. 343, no. 6, pp. 342-352, 2010.

A. Nayak, G. Achaiah and V. Reddy, "Rapid microwave assisted synthesis of hantzsch 1,4-dihydropyridines", Indian Journal of Heterocyclic Chemistry, vol. 18, no. 4, pp. 413-414, 2009.

A. Nayak, G. Achaiah and V. Reddy, "Microwave assisted synthesis and antimicrobial activity of 1,4-dihydropyridines", Indian Journal of Heterocyclic Chemistry, vol. 19, no. 2, pp. 193-194, 2009.

R. Rane, S. Naphade, P. Bangalore, M. Palkar, M. Shaikh and R. Karpoormath, "Synthesis of novel 4-nitropyrrole-based semicarbazide and thiosemicarbazide hybrids with antimicrobial and anti-tubercular activity", Bioorganic & Medicinal Chemistry Letters, vol. 24, no. 14, pp. 3079-3083, 2014.

M. El-Sharief, S. Abbas, K. El-Bayouki and E. El-Gammal, "Synthesis of thiosemicarbazones derived from N-(4-hippuric acid) thiosemicarbazide and different carbonyl compounds as antimicrobial agents", European Journal of Medicinal Chemistry, vol. 67, pp. 263-268, 2013.

M. Altıntop, Ö. Atlı, S. Ilgın, R. Demirel, A. Özdemir and Z. Kaplancıklı, "Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents", European Journal of Medicinal Chemistry, vol. 108, pp. 406-414, 2016.

N. Thanh, N. Giang, T. Quyen, D. Huong and V. Toan, "Synthesis and evaluation of in vivo antioxidant, in vitro antibacterial, MRSA and antifungal activity of novel substituted isatin N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazones", European Journal of Medicinal Chemistry, vol. 123, pp. 532-543, 2016.

R. Kumar, A. Idhayadhulla, A. Nasser and J. Selvin, "Synthesis and anticoagulant activity of a new series of 1,4-dihydropyridine derivatives", European Journal of Medicinal Chemistry, vol. 46, pp. 804-810, 2011.

H. Patel, S. Divatia and E. de Clercq, "Synthesis of some novel thiosemicarbazone derivatives having anti-cancer, anti-HIV as well as anti-bacterial activity", Indian Journal of Chemistry, vol. 52B, pp. 535-545, 2013.

T. Mosmann, "Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays". Journal of Immunological Methods, vol. 65, pp. 55–63 1983.

Full Text: PDF


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.



About IJSBAR | Privacy PolicyTerms & ConditionsContact UsDisclaimerFAQs

IJSBAR is published by (GSSRR).

 Plagiarism Policy