Author(s):
Janani C, Anjali Nayak, Paramita Das, Monisha S, Mahesh Chougule
Email(s):
anjaliangel84.pharma@gmail.com
DOI:
10.52711/0974-360X.2025.00303 
Address:
Janani C, Anjali Nayak*, Paramita Das, Monisha S, Mahesh Chougule
Krupanidhi College of Pharmacy, #12/1 Chikkabellandur, Carmelaram Post, Varthur Hobli, Bengaluru – 560035, Karnataka, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 5,
Year - 2025
ABSTRACT:
Hypertension affects a significant fraction of the global population and is widespread global health concern. Medical professionals frequently prescribe Calcium channel blockers as primary treatment for hypertension, due to its demonstrated efficacy and 1,4-dihydropyridine and it’s derivatives which are currently in use. The objective is to study antihypertensive effect of various analogues of 1,4-dihydropyridine derivatives with in-silico method of evaluation, synthesis and characterization. Ten derivatives were designed and docked on L-type calcium channel protein (PDB ID- 3LV3) using Autodock 1.5.7 and Biovia Discovery studio visualizer. The 5 derivatives of best binding energy were synthesized using Hantzsch method followed by characterization using IR, 1H NMR and MASS and assessments of antihypertensive activity pharmacologically by tail-cuff method using Nifedipine as standard drug. 1,4-dihydropyridine derivatives (DHP-01 to DHP-05) were synthesized and characterized. Nevertheless, a significant difference in lowering blood pressure was observed after comparing with standard nifedipine. The synthesized derivative DHP-02 was found to be effective as antihypertensive agent. Newly synthesized 1,4-dihydropyridine derivatives can be further studied for antihypertensive activity.
Cite this article:
Janani C, Anjali Nayak, Paramita Das, Monisha S, Mahesh Chougule. Integration of Molecular Docking Approaches with Experimental Synthesis: Evaluation of Novel 1,4-Dihydropyridine derivatives for Antihypertensive activity. Research Journal of Pharmacy and Technology. 2025;18(5):2115-0. doi: 10.52711/0974-360X.2025.00303
Cite(Electronic):
Janani C, Anjali Nayak, Paramita Das, Monisha S, Mahesh Chougule. Integration of Molecular Docking Approaches with Experimental Synthesis: Evaluation of Novel 1,4-Dihydropyridine derivatives for Antihypertensive activity. Research Journal of Pharmacy and Technology. 2025;18(5):2115-0. doi: 10.52711/0974-360X.2025.00303 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-5-26
REFERENCES:
1. Chitra SM, Anbu N, Uma KS. Antihypertensive activity of polyherbal siddha formulation veppampoo mathirai-A review. Research Journal of Pharmacy and Technology. 2022; 15(3): 1365-70. doi: http://dx.doi.org/10.52711/0974-360X.2022.00228
2. Takkar P, Singh B, Pani B, Kumar R. Design, synthesis and in silico evaluation of newer 1, 4-dihydropyridine based amlodipine bio-isosteres as promising antihypertensive agents. RSC advances. 2023; Nov 22; 13(48): 34239-48. doi: 10.1039/D3RA06387A
3. Bhavika D. Satone, Atul A. Deshmukh, Vaishali R. Undale. Preclinical Evaluation of Antihypertensive Activity of Combination of Herbs Extract in Wistar Rats. Research Journal of Pharmacy and Technology. 2020; 13(5): 2069-2075. doi: https://doi.org/10.5958/0974-360X.2020.00372.8
4. Bryzgalov A, Tolstikova T, Koshcheev B, Maksimov A. Synthesis new fluorinated 4-phenyl-1, 4-dihydropyridine derivatives, as perspective antiarrhythmic and antihypertensive drugs. Results in Chemistry. 2023 Jan 1; 5: 1-7. doi: https://doi.org/10.1016/j.rechem.2022.100705
5. Babu MN, Elumalai K, Srinivasan S, Eluri K, Elumalai M, Sivannan S. Synthesis and anticholinesterase activity of a novel series of acetazolamide condensed 1, 4-dihydropyridines. Carbon Resources Conversion. 2019Dec 1; 2(3): 191-7. doi: https://doi.org/10.1016/j.crcon.2019.10.002
6. Borah B, Patat M, Swain S, Chowhan LR. Recent advances and prospects in the transition‐metal‐free synthesis of 1, 4‐dihydropyridines. Chemistry Select. 2022 Jul 21; 7(27): 1-15. doi: https://doi.org/10.1002/slct.202202484
7. Bhaumik A, Reddy GV, Pasha SY, Nagababu SS. Synthetic Novel 1, 4-Dihydropyridine Derivatives Act as Potential Hepatoprotective Agent against CCl4 Induced Rat Hepatocytes. Journal of Pharmacy and Pharmacology. 2015; 3: 80-9. doi: https://doi.org/10.17265/2328-2150/2015.02.005
8. Santa-Helena E, da Costa Cabrera D, D'Oca MG, Scaini JL, de Oliveira MW, Werhli AV, et al. Long-chain fatty dihydropyridines: Docking calcium channel studies and antihypertensive activity. Life Sciences. 2020 Oct 15; 259: 1-11. doi: https://doi.org/10.1016/j.lfs.2020.118210
9. Szabo Í, M. Tóth O, Török Z, Varga DP, Menyhárt Á, Frank R, et al. The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization. British Journal of Pharmacologhy. 2019 May; 176(9): 1222-34. doi: https://doi.org/10.1111/bph.14611
10. Khot S, Auti PB, Khedkar SA. Diversified synthetic pathway of 1, 4-dihydropyridines: a class of pharmacologically important molecules. Mini Reviews in Medicinal Chemistry. 2021 Feb 1; 21(2): 135-49. doi: https://doi.org/10.2174/1389557520666200807130215
11. Datar PA, Auti PB. Design and synthesis of novel 4-substituted 1, 4-dihydropyridine derivatives as hypotensive agents. Journal of Saudi Chemical Society. 2016; Sep 1; 20(5): 510-6. doi: https://doi.org/10.1016/j.jscs.2012.08.003
12. Milkovic L, Vukovic T, Zarkovic N, Tatzber F, Bisenieks E, Kalme Z, Bruvere I, Ogle Z, Poikans J, Velena A, Duburs G. Antioxidative 1, 4-dihydropyridine derivatives modulate oxidative stress and growth of human osteoblast-like cells in vitro. Antioxidants. 2018 Sep 19; 7(9): 123. doi: https://doi.org/10.3390/antiox7090123
13. Gadotti VM, Bladen C, Zhang FX, Chen L, Gündüz MG, Şimşek R, et al. Analgesic effect of a broad-spectrum dihydropyridine inhibitor of voltage-gated calcium channels. Pflügers Archiv-European Journal of Physiology. 2015 Aug 19; 467: 2485-93. doi: https://doi.org/10.1007/s00424-015-1725-1
14. Ramírez-San Juan E, Soriano-Ursúa MA, Espinosa-Raya J, Correa-Basurto J, Trujillo-Ferrara JG, Miranda-Ruvalcaba R, et al. Anticonvulsant effects of bis-1, 4-dihydropyridines and the probable role of L-type calcium channels suggested by docking simulations. Medicinal Chemistry Research. 2014 Jun 28; 23: 5149-59. doi: https://doi.org/10.1007/s00044-014-1083-0
15. Idhayadhulla A, Kumar RS, Nasser AJ, Kavimani S, Indhumathy S. Anti-inflammatory activity of new series of 1, 4-dihydropyridine derivatives. Pharmaceutical Chemistry Journal. 2015 Oct 31; 49: 463-6. doi: https://doi.org/10.1007/s11094-015-1305-x
16. Olejníková P, ŠVORC Ľ, Olšovská D, Panáková A, Vihonská Z, Kovaryová K, et al. Antimicrobial activity of novel C2-substituted 1, 4-dihydropyridine analogues. Scientia Pharmceutica. 2014 Jan 12; 82(2): 221-32. doi: https://doi.org/10.3797/scipharm.1311-04
17. Ling Y, Hao ZY, Liang D, Zhang CL, Liu YF, Wang Y. The expanding role of pyridine and dihydropyridine scaffolds in drug design. Drug Design, Development and Therapy. 2021 Oct 13; 15: 4289-338. doi: https://doi.org/10.2147/DDDT.S329547
18. Chatki PK, Tabassum S. Analytical Methods of Dihydropyridines Based Calcium Channel Blockers - Amlodipine, Lacidipine, Isradipine, Nifedipine, Felodipine, Cilnidipine and its related formulations: A Review. Asian Journal of Research in Chemistry. 2021; 14(3): 221-4. doi: http://dx.doi.org/10.52711/0974-4150.2021.00039
19. Wu L, Lin W, Liao Q, Wang H, Lin C, Tang L, et al. Calcium channel blocker nifedipine suppresses colorectal cancer progression and immune escape by preventing NFAT2 nuclear translocation. Cell Reports. 2020; Oct 27; 33(4): 1-13. doi: https://doi.org/10.1016/j.celrep.2020.108327
20. Pawar S, Kulkarni C, Gadade P, Pujari S, Kakade S, Rohane SH, et al. Molecular Docking using different Tools. Asian Journal of Pharmaceutical Research. 2023; Dec 1; 13(4): 292-6. http://dx.doi.org/10.52711/2231-5691.2023.00053
21. Kumar RS, Basha SN, Nallasivan PK, Solomon WD, Venkatnarayanan R. Computer aided docking studies on antiviral drugs for bird flu. Asian Journal of Research in Chemistry. 2010; 3(2): 370-3.
22. Patadiya N, Vaghela V. Design, in-silico ADME Study and molecular docking study of novel quinoline-4-on derivatives as Factor Xa Inhibitor as Potential anti-coagulating agents. Asian Journal of Pharmaceutical Research. 2022; Feb 6; 12(3): 207-11. doi: http://dx.doi.org/10.52711/2231-5691.2022.00034
23. Mishra AP, Meel RK. Synthesis and Pharmacological Evaluation of the derivatives of 1,4-dihydropyridine: A Pleiotropic Molecule with Antiulcer activity. Research Journal of Pharmacy and Technology. 2023; 16(2): 561-5. https://doi.org/10.52711/0974-360X.2023.00096
24. Nayak A, Das P, Das AK. Synthesis and Evaluation of Amide Codrug of Ibuprofen and Amlodipine for Dual Inhibition of Inflammation and Hypertension. Research Journal of Pharmacy and Technology. 2023; 16(8): 3957-63. doi: http://dx.doi.org/10.52711/0974-360X.2023.00651
25. Sabareesh M, Yanadaiah JP, Chandra Sekhar KB. Formulation Development, Ex vivo Evaluation and In vivo Antihypertensive study of Losartan Potassium Loaded Nanoproniosomal Gel: A Novel Vesicular Approach for Transdermal Delivery. Research Journal of Pharmacy and Technology. 2021; 14(3): 1423-1430. doi: http://dx.doi.org/10.5958/0974-360X.2021.00254.7