Interaction of Bioactive Pyrazolo[4,3-a]acridines with Human Serum Albumin

Document Type : Research Article

Authors

Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, I.R. Iran

Abstract

Several heterocyclic bioactive fluorescent 3-alkyl-3H-pyrazolo[4,3-a]acridin-11-carbonitriles were conveniently synthesized from the reaction of 1-alkyl-1H-indazoles with different aryl acetonitrile in basic methanol solution in good yields. The interactions of 3H-pyrazolo[4,3-a]acridin-11-carbonitriles with Human Serum Albumin (HSA) were studied by fluorescence spectroscopy. The binding of 3-alkyl-3H-pyrazolo[4,3-a]acridin-11-carbonitriles quenches the HSA fluorescence, revealing a 1:1 interaction with a binding constant of about 1.28 × 103 – 1.85 × 103 M-1.A decrease in fluorescence intensity at 339 nm, when excited at 295 nm, is attributed to changes in the environment of the protein fluorophores caused by the presence of the ligand. The results show that pyrazolo[4,3-a]acridines with R=propyl, butyl, isobutyl and R'=chlorine substituents have suitable thermodynamic and binding parameters with  HSA.
 

Keywords

Main Subjects

References

[1] Kratz F, Elsadek B., Clinical Impact of Serum Proteins on Drug Delivery, J. Control. Release., 161:429-445 (2012).
[2] Varshney A., Sen P., Ahmad E., Rehan M., Subbarao N., Khan R.H., Ligand Binding Strategies of Human Serum Albumin: How Can the Cargo be Utilized?, Chirality, 22:77-87 (2010).
[3] Yang F., Zhang Y., Liang H., Interactive Association of Drugs Binding to Human Serum Albumin, Int. J. Mol. Sci., 15:3580-3595 (2014).
[4]  Zaidi N., Ahmad E., Rehan M., Rabbani G., Ajmal M.R., Zaidi Y., Subbarao N., Khan R.H., Biophysical Insight Into Furosemide Binding to Human Serum Albumin: A Study to Unveil its Impaired Albumin Binding in Uremia, J. Phys. Chem. B., 117:2595-2604 (2013).
[5] Meireles L, Gur M, Bakan A, Bahar I., Pre‐Existing Soft Modes of Motion Uniquely Defined by Native Contact Topology Facilitate Ligand Binding to Proteins, Protein Sci., 20:1645-1658 (2011).
[6] Sato T., Saito Y., Chikuma M., Saito Y., Nagai S., Determination of Albumin in Bronchoalveolar Lavage Fluid by Flow-Injection Fluorometry Using Chromazurol S, Biol. Pharm. Bull., 31:336-339 (2008).
[7] Jones L.J., Haugland R.P., Singer V.L., Development and Characterization of the NanoOrange® Protein Quantitation Assay: A Fluorescence-Based Assay of Proteins in Solution. Biotechniques, 34:850-861 (2003).
[8] Meneyrol J., Follmann M., Lassalle G., Wehner V., Barre G., Rousseaux T., Altenburger J.M., Petit F., Bocskei Z., Schreuder H., Alet N., 5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl) benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl] Amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor., J. Med. Chem., 56:9441-9456 (2013).
[9] Grabowski Z.R., Rotkiewicz K., Rettig W., Structural Changes Accompanying Intramolecular Electron Transfer: Focus on Twisted Intramolecular Charge-Transfer States and Structures., Chem. Rev., 103:3899-4032     
(2003).
[10] Mohammadi Z.G., Mousavi S., Lashgari N., Badiei A., Shakiba Monireh, Application of Sulfonic Acid Functionalized Nanoporous Silica (sba-pr-so3h) in the Green One-Pot Synthesis of Polyhydroacridine Libraries., Iran. J. Chem. Chem. Eng. (IJCCE), 32(4): 9-16 (2013).
[11] Marjani A.P., Khalafy J., Chitan M., Mahmoodi S., Microwave-Assisted Synthesis of Acridine-1,8(2h,5h)-diones via a One-Pot, Three Component Reaction., Iran. J. Chem. Chem. Eng (IJCCE), 36(2): 1-6 (2017).
[12] Karagöz F., Güney O., Kandaz M., Bilgiçli A.T., Acridine-Derivated Receptor for Selective Mercury Binding Based on Chelation-Enhanced Fluorescence Effect., J. Lumin., 132:2736-2740  (2012).
[13] Babu V.S, Reddy H.K. Rare Earth Nitrate Complexes with an ONO Schiff Base Ligand: Spectral, Thermal, Luminescence and Biological Studies., Iran. J. Chem. Chem. Engin. (IJCCE), 36(4): 101-109 (2017).
[14] Kaya M., Yıldırır Y., Çelik G.Y., Synthesis, Characterization, and In Vitro Antimicrobial and Antifungal Activity of Novel Acridines, Pharm. Chem. J., 48:722-726 (2015).
[15] Denny W.A., Acridine Derivatives as Chemotherapeutic Agents, Curr. Med. Chem., 9:1655-1665 (2002).
[16] Goodell J.R., Madhok A.A., Hiasa H., Ferguson D.M., Synthesis and Evaluation of Acridine-and Acridone-Based Anti-Herpes Agents with Topoisomerase Activity, Bioorg. Med. Chem., 14:5467-5480 (2006).
[17] Tabarrini O., Manfroni G., Fravolini A., Cecchetti V., Sabatini S., De Clercq E., Rozenski J., Canard B., Dutartre H., Paeshuyse J., Neyts J., Synthesis and Anti-BVDV Activity of Acridones As New Potential Antiviral Agents 1, J. Med. Chem., 49:2621-2627 (2006).
[18] Kukowska-Kaszuba M., Dzierzbicka K., Synthesis and Structure-Activity Studies of Peptide-Acridine/ Acridone Conjugates, Curr. Med. Chem., 14: 3079-3104 (2007).
[19] Winter R.W., Kelly J.X., Smilkstein M.J., Dodean R., Hinrichs D., Riscoe M.K., Antimalarial Quinolones: Synthesis, Potency, and Mechanistic Studies, Exp. Parasitol., 118:487-497 (2008).
[20] Joshi A.A., Viswanathan C.L., Recent Developments in Antimalarial Drug Discovery, Antiinfect. Agents Med. Chem., 5:105-122 (2006).
[21] Belmont P., Bosson J., Godet T., Tiano M., Acridine and Acridone Derivatives, Anticancer Properties and Synthetic Methods: Where are We Now?, Anticancer Agents Med. Chem., 7: 139-169 (2007).
[22] Kamal A., Srinivas O., Ramulu P., Ramesh G., Kumar P.P., Synthesis of C8-Linked Pyrrolo [2, 1-c] [1, 4] Benzodiazepine-Acridone/Acridine Hybrids as Potential DNA-Binding Agents, Bioorg. Med. Chem. Lett., 14:4107-4111 (2004).
[23] Demeunynck M., Antitumour Acridines, Expert Opin. Ther. Pat., 14:55-70 (2004).
[24] Niemira M, Dastych J, Mazerska Z., Pregnane X Receptor Dependent up-Regulation of CYP2C9 and CYP3A4 in Tumor Cells by Antitumor Acridine Agents, C-1748 and C-1305, Selectively Diminished under Hypoxia, Biochem. Pharmacol., 86: 231-241(2013).
[25] Daghigh L.R, Pordel M., Davoodnia A., Synthesis of New Fluorescent Pyrazolo [4, 3-a] Acridine Derivatives Having Strong Antibacterial Activities, J. Chem. Res., 38: 202-207 (2014).
[26] Rahmani Z., Pordel M., Davoodnia A., Design, Synthesis, Fluorescence Properties and Antibacterial Activities of New 8-Chloro-3-Alkyl-3H-Pyrazolo[4,3-a]acridine-11-Carbonitriles, Bull. Korean Chem., 35: 551-556 (2014).
[27] Pakjoo V., Roshani M., Pordel M., Hoseini T., Synthesis of New Fluorescent Compounds from 5-Nitro-1H-Indazole, Arkivoc. 9: 195-203 (2012).
[28] Bouissane L., El Kazzouli S., Léger J.M., Jarry C., Rakib E.M., Khouili M., Guillaumet G., New and Efficient Synthesis of bi-and Trisubstituted Indazoles, Tetrahedron, 61: 8218-8225 (2005).
[29] Nitzan A., Jortner J., Kommandeur J., Drent E., A Quantum Mechanical Analogue of the Stern-Volmer Equation, Chem. Phys. Lett., 9: 273-278 (1971).
[30] Boaz H., Rollefson, G.K., The Quenching of Fluorescence. Deviations from the Stern-Volmer Law, J. Am. Chem. Soc., 72: 3435-3443 (1950).
[31] Lakowicz J.R., Weber G., Quenching of Protein Fluorescence by Oxygen. Detection of Structural Fluctuations in Proteins on the Nanosecond Time Scale, Biochemistry, 12: 4171-4170 (1973).
[32] Gao H., Lei L., Liu J., Kong Q., Chen X, Hu Z., The Study on the Interaction between Human Serum Albumin and a New reagent with Antitumour Activity by Spectrophotometric Methods, J. Photochem. Photobiol. A: Chem., 167: 213-221 (2004).
[33] Lakowicz J.R., “Principles of Fluorescence Spectroscopy”, 2nd ed Kluwer Academic/Plenum Publishers New York NY USA, (1999).
Iranian Journal of Chemistry and Chemical Engineering
Volume 36, Issue 6 - Serial Number 86
November and December 2017
Pages 85-91

Files

Share

How to cite

Statistics