Vivek B. Panchabhai, Santosh R. Butle, Parag G. Ingole
Vivek B. Panchabhai*, Santosh R. Butle, Parag G. Ingole
Department of Pharmaceutical Chemistry, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Nanded-431606, Maharashtra, India.
Volume - 14,
Issue - 7,
Year - 2021
We report a novel scaffold of N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives with potent antibacterial activity by targeting this biotin carboxylase enzyme. The series of eighteen N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives were synthesized, characterized and further molecular docking studied to determine the mode of binding and energy changes with the crystal structure of biotin carboxylase (PDB ID: 2V58) was employed as the receptor with compounds 6a-r as ligands. The results obtained from the simulation were obtained in the form of dock score; these values represent the minimum energies. Compounds 6d, 6l, 6n, 6o, 6r and 6i showed formation of hydrogen bonds with the active site residues and van Der Walls interactions with the biotin carboxylase enzyme in their molecular docking studies. This compound can be studied further and developed into a potential antibacterial lead molecule.
Cite this article:
Vivek B. Panchabhai, Santosh R. Butle, Parag G. Ingole. Synthesis, characterization and molecular docking studies on some new N-substituted 2-phenylpyrido[2,3-d]pyrimidine derivatives. Research Journal of Pharmacy and Technology. 2021; 14(7):3846-4. doi: 10.52711/0974-360X.2021.00667
Vivek B. Panchabhai, Santosh R. Butle, Parag G. Ingole. Synthesis, characterization and molecular docking studies on some new N-substituted 2-phenylpyrido[2,3-d]pyrimidine derivatives. Research Journal of Pharmacy and Technology. 2021; 14(7):3846-4. doi: 10.52711/0974-360X.2021.00667 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-7-64
1. W. H. Organization, Antimicrobial resistance: global report on surveillance. World Health Organization.
2. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confrontingthe challenges of antibacterial discovery. Nature Reviews Drug Discovery. 2007; 6 (1): 29-40.
3. Clardy J, Fischbach MA, Currie CR. The natural history of antibiotics. Current Biology. 2009; 19 (11): 437- 441.
4. Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nature Reviews Microbiology. 2010; 8 (6): 423-35.
5. Amgaokar Y.M., Chikhale R.V., Lade U.B., Biyani D.M., Umekar M.J., Design, formulation and evaluation of transdermal drug delivery system of budesonide. Digest Journal of Nanomaterials. 2011; 6 (2): 475-497.
6. Lade U.B., Amgaonkar Y.M., Chikhale R.V., Biyani D.M., Umekar M.J., Design, formulation and evaluation of transdermal drug delivery system of budesonide. Pharmacology Pharmacy. 2011; 2(03): 199-211.
7. Choi-Rhee E, Cronan JE. The biotin carboxylase-biotin carboxyl carrier protein complex of Escherichia coli acetyl-CoA carboxylase. Journal of Biological Chemistry. 2003; 278 (33): 30806-30812.
8. Miller JR, Dunham S, Mochalkin I, Banotai C, Bowman M, Buist S, et al. A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore. Proceedings of the National Academy of Sciences. 2009; 106 (6): 1737-1742.
9. Mochalkin I, Miller JR, Narasimhan L, Thanabal V, Erdman P, Cox PB, et al. Discovery of antibacterial biotin carboxylase inhibitors by virtual screening and fragment based approaches. ACS Chemical Biology. 2009; 4(6): 473-483.
10. Chikhale R., Menghani S., Babu R., Bansode R., Bhargavi G., Karodia N., Rajasekharan M., Paradkar A., Khedekar P., Development of selective DprE1 inhibitors: Design, synthesis, crystal structure and antitubercular activity of benzothiazolylpyrimidine-5-carboxamides. European Journal of Medicinal Chemistry. 2015; 96: 30-46.
11. Chikhale R.V., Pant A.M., Menghani S.S., Khedekar P.B., Development of dual inhibitors targeting DprE1 and AHAS for treatment of Mycobacterium tuberculosis infection. BMC Infectious Diseases. 2014; 14 (3): E24.
12. Chikhale R.V., Pant A.M., Menghani S.S., Wadibhasme P.G., Khedekar P.B., Facile and efficient synthesis of benzoxazole derivatives using novel catalytic activity of PEG-SO 3 H, Arabian Journal of Chemistry. 2014; 2 (5): 715-725.
13. Huron D.R., Gorre M.E., Kraker A.J., Sawyers C.L., Rosen N., Moasser M.M., A novel pyridopyrimidine inhibitor of abl kinase is a picomolar inhibitor of Bcr-abl-driven K562 cells and is effective against STI571-resistant Bcr-abl mutants, Clinical Cancer Research. 2003; 9 (4): 1267-1273.
14. Nakayama K., Kawato H., Watanabe J., Ohtsuka M.,. Yoshida K.-i, Yokomizo Y., Sakamoto A., Kuru N., Ohta T., Hoshino K., MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3: Optimization of potency in the pyridopyrimidine series through the application of a pharmacophore model. Bioorganic and Medicinal Chemistry Letters. 2004; 14(2): 475-479.
15. Zheng G.Z., Mao Y., Lee C.-H., Pratt J.K., Koenig J.R., Perner R.J., Cowart M.D., Gfesser G.A., McGaraughty S., Chu K.L., Adenosine kinase inhibitors: polar 7-substitutent of pyridopyrimidine derivatives improving their locomotor selectivity. Bioorganic and Medicinal Chemistry Letters. 2003; 13(18): 3041-3044.
16. Saurat T., Buron F., Rodrigues N., de Tauzia M.L., Colliandre L., Bourg S., Bonnet P., Guillaumet G., Akssira M., Corlu A., Guillouzo C., Berthier P., Rio P., Jourdan M.L., Benedetti H., Routier S., Design, Synthesis, and Biological Activity of Pyridopyrimidine Scaffolds as Novel PI3K/mTOR Dual Inhibitors. Journal of Medicinal Chemistry. 2014; 57 (3): 613-631.
17. Labadie S., Barrett K., Blair W.S., Chang C., Deshmukh G., Eigenbrot C., Gibbons P., Johnson A., Kenny J.R., Kohli P.B., Liimatta M., Lupardus P.J., Shia S., Steffek M., Ubhayakar S., van Abbema A., Zak M., Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors, Bioorg. Med. Chem. Lett. 2013; 23(21): 5923-5930.
18. Mizenina O.A., Moasser M.M., S-phase inhibition of cell cycle progression by a novel class of pyridopyrimidine tyrosine kinase inhibitors. Cell Cycle. 2004; 3(6): 794-801.
19. Rajesh S.M., Kumar R.S., Libertsen L.A., Perumal S., Yogeeswari P., Sriram D., A green expedient synthesis of pyridopyrimidine-2-thiones and their antitubercular activity, Bioorganic and Medicinal Chemistry Letters. 2011; 21(10): 3012-3016.
20. Chikhale R.V., Barmade M.A., Murumkar P.R., Yadav M.R., Overview of the development of DprE1 inhibitors for combating the menace of tuberculosis. Journal of Medicinal Chemistry. 2018; 61(19): 8563-8593.
21. Saundane A.R., Vijaykumar K., Vaijinath A.V., Walmik P., Synthesis, antimicrobial and antioxidant activities of some new indole derivatives containing pyridopyrimidine and pyrazolopyridine moieties. Medicinal Chemistry Research. 2013; 22 (2): 806-817.
22. Dave C.G., Shukla M.C., Pyridopyrimidines: Part IX-Synthesis and antibacterial activity of 2-methylthio-6-phenylazo-5, 7-dimethylpyrido [2, 3-d] pyrimidin-4 (3H)-ones, Indian Journal of Chemistry. 2000; 39B: 210-214.
23. Ribble W., Hill W.E., Ochsner U.A., Jarvis T.C., Guiles J.W., Janjic N., Bullard J.M., Discovery and analysis of 4H-pyridopyrimidines, a class of selective bacterial protein synthesis inhibitors, Antimicrob Agents Chemother. 2010; 54(11): 4648-4657.
24. Guiles J.W., Toro A., Ochsner U.A., Bullard J.M., Development of 4H-pyridopyrimidines: a class of selective bacterial protein synthesis inhibitors, Organic and Medicinal Chemistry Letters. 2012; 2 (1): 5.
25. Ali El Remaily M.A.E.A., El Hady O.M., Salah Abo Zaid H., Abd El Raheem E.M.M., Synthesis and in vitro Antibacterial Activity of Some Novel Fused Pyridopyrimidine Derivatives. Journal of Heterocyclic Chemistry. 2016; 53: 1304-1309.
26. Silvers M.A., Robertson G.T., Taylor C.M., Waldrop G.L., Design, synthesis, and antibacterial properties of dual-ligand inhibitors of acetyl-CoA carboxylase. Journal of Medicinal Chemistry. 2014; 57(21): 8947-8959.
27. Brylinski M., Waldrop G.L., Computational Redesign of Bacterial Biotin Carboxylase Inhibitors Using Structure-Based Virtual Screening of Combinatorial Libraries. Molecules. 2014; 19(4): 4021-4045.
28. Chikhale R, Thorat S, Pant A, Jadhav A, Thatipamula KC, Bansode R, et al. Design, synthesis and pharmacological evaluation of pyrimidobenzothiazole-3-carboxylate derivatives as selective L-type calcium channel blockers. Bioorganic and Medicinal Chemistry. 2015; 23(20): 6689-6713.
29. Chakravarty S., Dugar S., Perumattam J.J., Schreiner G.F., Liu D.Y., Lewicki J.A., Quinazoline derivatives as medicaments, United States Patent US 6476031, 2002.
30. Li J.J., Fischer-Speier esterification, Name Reactions, Springer., 2003; 139-139.