Abstract
Small molecules have potential usage in cancer therapy due to their remarkable potency of disarranging the natural structure of nucleic acids. In this study, two complexes [Pt(NH3)2(IBgly)]NO3 (1) and [Pt(bipy)(IBgly)]NO3 (2) based on Pt(II), N-isobutylglycine (IBgly), 2,2′-bipyridine, and ammonia were prepared and characterized by spectroscopic methods. Pharmacokinetic ADME data, absorption, distribution, metabolism, excretion, and bioavailability radar showed two complexes can be introduced for Pt-based anti-cancer drugs. Mechanism of tumor inhibition and DNA interaction of these compounds was studied by UV–Vis, fluorescence, and CD spectroscopies. Also, thermodynamic parameters and the binding constants were calculated through absorption measurements. The fluorescence data showed that a static quenching mechanism occurred for both complexes with a binding constant and binding affinity towards DNA (Kb ≈ 3500 M−1 and kq ≈ 2.1 × 1011 M−1 s−1). The thermodynamic parameters indicated electrostatic approaching and groove binding were more feasible than intercalation mode between Pt(II) complexes and DNA. CD spectra indicated the increasing intensity of the positive band and the negative band decreasing. Density functional theory calculations confirmed the experimental data and determined the quantum chemical descriptors including total energy, hardness, chemical potential, electrophilicity, electronegativity, etc. According to this, the binding tendency of these compounds with DNA could be predicted. Further, molecular docking studies were also performed. Docking studies revealed that the desolvation, hydrogen, and electrostatic binding were effective for the interaction between complexes and DNA with binding energy (− 10.44 and − 9.57 kcal/mol) for complexes 1 and 2, respectively, which is mainly of partially electrostatic and groove binding type. The cytotoxic activity of Pt complexes was examined against human colon cancer cell line which indicated good activity with IC50 values of (41.66 and 47.30 μM) for both complexes after 72 h, respectively. Also, they demonstrated more inhibitory effects compared to carboplatin.
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Abbreviations
- ADME:
-
Absorption, distribution, metabolism, and excretion
- BBB:
-
Blood–brain barrier
- bipy:
-
2,2′-Bipyridine
- CT-DNA:
-
Calf thymus DNA
- EB:
-
Ethidium bromide
- CD:
-
Circular dichroism
- DFT:
-
Density functional theory
- FMOs:
-
Frontier molecular orbitals
- IBgly:
-
N-Isobutylglycine
- K:
-
Equilibrium constant
- Kb :
-
Binding constant
- kq :
-
Biomolecular quenching constant
- K sv :
-
Stern–Volmer quenching constant
- MEP:
-
Molecular electrostatic potential
- NBO:
-
Natural bond order
- QCDs:
-
Quantum chemical descriptors
- PGP:
-
P-glycoprotein
- PDB:
-
Protein data bank
- Tris-buffer:
-
Tris(hydroxymethyl)aminomethane hydrochloride
References
Akbay N, Seferoğlu Z, Gök E (2009) Fluorescence interaction and determination of calf thymus DNA with two ethidium derivatives. J Fluoresc 19(6):1045–1051. https://doi.org/10.1007/s10895-009-0504-9
Albani JR (2007) Principles and applications of fluorescence spectroscopy. Blackwell Science Publications, Hoboken
Aminzadeh M, Saeidifar M, Mansouri-Torshizi H (2020) Synthesis, characterization, DNA binding, cytotoxicity, and molecular docking approaches of Pd(II) complex with N, O-donor ligands as a novel potent anticancer agent. J Mol Struct 1215:128212. https://doi.org/10.1016/j.molstruc.2020.128212
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
Castro PM, Jagodzinski PW (1991) FTIR and Raman spectra and structure of Cu(NO3)+ in aqueous solution and acetone. Spectrochim Acta Part A 47(12):1707–1720. https://doi.org/10.1016/0584-8539(91)80008-7
Clark DE, Pickett SD (2000) Computational methods for the prediction of ‘drug-likeness.’ Drug Discov Today 5(2):49–58. https://doi.org/10.1016/S1359-6446(99)01451-8
Cohen SM, Lippard SJ (2001) Cisplatin: from DNA damage to cancer chemotherapy. Prog Nucleic Acid Res Mol Biol 67:93–103. https://doi.org/10.1016/S0079-6603(01)67026-0
Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7(1):1–3. https://doi.org/10.1038/srep42717
Dennington R, Keith TA, Millam JM (2016) GaussView 6.0. 16. Semichem Inc, Shawnee Mission
Drew HDK, Pinkard FW, Wardlaw W, Cox EG (1932) The structure of the isomeric diamminoplatinous chlorides. Discovery of a third isomeride. J. Chem. Soc., 988-1004 https://doi.org/10.1039/JR9320000988
Eslami Moghadam M, Saidifar M, Divsalar A, Mansouri-Torshizi H, Saboury AA, Farhangian H, Ghadamgahi M (2016) Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt(II) and Pd(II) complexes of glycine derivatives with calf thymus DNA. J Biomol Struct Dyn 34(1):206–222. https://doi.org/10.1080/07391102.2015.1015056
Fan W, Yung B, Huang P, Chen X (2017) Nanotechnology for multimodal synergistic cancer therapy. Chem Rev 117(22):13566–13638. https://doi.org/10.1021/acs.chemrev.7b00258
Farhangian H, Eslami Moghadam M, Divsalar A, Rahiminezhad A (2017) Anticancer activity of novel amino acid derivative of palladium complex with phendione ligand against of human colon cancer cell line. JBIC J Biol Inorg Chem 22(7):1055–1064. https://doi.org/10.1007/s00775-017-1483-y
Fischer G, Cao X, Cox N, Francis M (2005) The FT-IR spectra of glycine and glycylglycine zwitterions isolated in alkali halide matrices. Chem Phys 313(1–3):39–49. https://doi.org/10.1016/j.chemphys.2004.12.011
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR et al (2009) Gaussian 09, Revision D.01. Gaussian, Inc, Wallingford
Fugger J, Tien JM, Hunsberger IM (1955) The preparation of substituted hydrazines. I. Alkylhydrazines via alkylsydnones1. J Am Chem Soc 77(7):1843–1848. https://doi.org/10.1021/ja01612a039
Ghalandari B, Poursoleiman A, Fekri M, Komeili A, Divsalar A, Eslami Moghadam M, Kamrava SK, Saboury AA (2019) Biological evaluations of newly-designed Pt(II) and Pd(II) complexes using spectroscopic and molecular docking approaches. J Biomol Struct Dyn 37(13):3422–3433. https://doi.org/10.1080/07391102.2018.1516164
Greene RF, Pace CN (1974) Urea and guanidine hydrochloride denaturation of ribonuclease, lysozyme, α-chymotrypsin, and β-lactoglobulin. J Biol Chem 249(17):5388–5393. https://doi.org/10.1016/S0021-9258(20)79739-5
He C, Liu X, Jiang Z, Geng S, Ma H, Liu B (2019) Interaction mechanism of flavonoids and α-glucosidase: experimental and molecular modelling studies. Foods 8(9):355. https://doi.org/10.3390/foods8090355
Hoffman BL, Schorge JO, Schaffer JI, Halvorson LM, Bradshaw KD, Corton MM (2016) Williams gynecology. The McGraw-Hill education, New York
Hosseinzadeh S, Eslami Moghadam M, Sheshmani S, Shahvelayati AS (2020) Some new anticancer platinum complexes of dithiocarbamate derivatives against human colorectal and pancreatic cell lines. J Biomol Struct Dyn 38(8):2215–2228. https://doi.org/10.1080/07391102.2019.1627909
Husain MA, Ishqi HM, Sarwar T, Rehman SU, Tabish M (2017) Interaction of indomethacin with calf thymus DNA: a multi-spectroscopic, thermodynamic and molecular modelling approach. MedChemComm 8(6):1283–1296. https://doi.org/10.1039/C7MD00094D
Iakovidis A, Hadjiliadis N (1994) Complex compounds of platinum(II) and (IV) with amino acids, peptides and their derivatives. Coord Chem Rev 135:17–63. https://doi.org/10.1016/0010-8545(94)80064-2
Imaz I, Rubio-Martinez M, An J, Sole-Font I, Rosi NL, Maspoch D (2011) Metal–biomolecule frameworks (MBioFs). Chem Commun 47(26):7287–7302. https://doi.org/10.1039/C1CC11202C
Imran M, Kondratyuk T, Bélanger-Gariepy F (2019) New ternary platinum(II) dithiocarbamates: synthesis, characterization, anticancer, DNA binding and DNA denaturing studies. Inorg Chem Commun 103:12–20. https://doi.org/10.1016/j.inoche.2019.02.007
Kieft JA, Nakamoto K (1967) Infrared spectra of some platinum (II) glycine complexes. J Inorg Nucl Chem 29(10):2561–2568. https://doi.org/10.1016/0022-1902(67)80181-7
Kurita N, Kobayashi K (2000) Density functional MO calculation for stacked DNA base-pairs with backbones. Comput Chem 24(3–4):351–357. https://doi.org/10.1016/S0097-8485(99)00071-6
Lakowicz JR (2006) Principles of fluorescence spectroscopy, 3rd edn. Springer Publications, New York
Latha AA, Anbuchezhiyan M, Kanakam CC, Selvarani K (2017) Synthesis and characterization of γ-glycine—a nonlinear optical single crystal for optoelectronic and photonic applications. Mater Sci 35(1):140–150. https://doi.org/10.1515/msp-2017-0031
Lehninger AL, Nelson DL, Cox MM, Cox MM (2005) Lehninger principles of biochemistry. Macmillan, London
Levine IN (2009) Physical chemistry, 6th edn. McGraw-Hill Education, New York
Liang B, Huo S, Ren Y, Sun S, Cao Z, Shen S (2015) A platinum(IV)-based metallointercalator: synthesis, cytotoxicity, and redox reactions with thiol-containing compounds. Trans Met Chem 40(1):31–37. https://doi.org/10.1007/s11243-014-9886-x
Liu HK, Sadler PJ (2011) Metal complexes as DNA intercalators. Acc Chem Res 44(5):349–359. https://doi.org/10.1021/ar100140e
Liu Y, Tian H, Xu L, Zhou L, Wang J, Xu B, Liu C, Elding LI, Shi T (2019) Investigations of the kinetics and mechanism of reduction of a carboplatin Pt(IV) prodrug by the major small-molecule reductants in human plasma. Int J Mol Sci 20(22):5660. https://doi.org/10.3390/ijms20225660
Mansouri-Torshizi H, Zareian-Jahromi S, Abdi K, Saeidifar M (2019) Nonionic but water soluble, [Glycine–Pd–Alanine] and [Glycine–Pd–Valine] complexes. Their synthesis, characterization, antitumor activities and rich DNA/HSA interaction studies. J Biomol Struct Dyn 37(13):3566–3582. https://doi.org/10.1080/07391102.2018.1520647
Miskowski VM, Houlding VH, Che CM, Wang Y (1993) Electronic spectra and photophysics of platinum(II) complexes with alpha-diimine ligands. Mixed complexes with halide ligands. Inorg Chem 32(11):2518–2524. https://doi.org/10.1021/ic00063a052
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2019) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30(16):2785–2791. https://doi.org/10.1002/jcc.21256
Nakamoto K (2009) Infrared and Raman spectra of inorganic and coordination compounds part B: applications in coordination, organometallic, and bioinorganic chemistry, 6th edn. Wiley, New York
Oun R, Moussa YE, Wheate NJ (2018) The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans 47(19):6645–6653. https://doi.org/10.1039/C8DT00838H
Pearson RG (1986) Absolute electronegativity and hardness correlated with molecular orbital theory. Proc Natl Acad Sci USA 83(22):8440–8441. https://doi.org/10.1073/pnas.83.22.8440
Ramezani N, Eslami Moghadam M, Behzad M (2021a) Investigating the anticancer properties of the two new platinum complexes with iso-and tert-pentylglycine by the DFT, molecular docking, and ADMET assessment and experimental confirmations. JBIC J Biol Inorg Chem 26(2):283–298. https://doi.org/10.1007/s00775-021-01851-1
Ramezani N, Eslami Moghadam M, Behzad M, Zolghadri S (2021b) Two new oral candidates as anticancer platinum complexes of 1,3-dimethyl pentyl glycine ligand as doping agents against breast cancer. Spectrochim Acta Part A 251:119415–119428. https://doi.org/10.1016/j.saa.2020.119415
Ramya KS, Iqbal S, Gunasekaran K, Radha A (2018) Anticancer potentials of quassinoids from Simarouba glauca–docking and ADME analysis. Res J Life Sci 4(5):218–230
Raudenska M, Balvan J, Fojtu M, Gumulec J, Masarik M (2019) Unexpected therapeutic effects of cisplatin. Metallomics 11(7):1182–1199. https://doi.org/10.1039/c9mt00049f
Rehman SU, Sarwar T, Husain MA, Ishqi HM, Tabish M (2015a) Studying non-covalent drug–DNA interactions. Arch Biochem Biophys 576:49–60. https://doi.org/10.1016/j.abb.2015.03.024
Rehman SU, Sarwar T, Ishqi HM, Husain MA, Hasan Z, Tabish M (2015b) Deciphering the interactions between chlorambucil and calf thymus DNA: a multi-spectroscopic and molecular docking study. Arch Biochem Biophys 566:7–14. https://doi.org/10.1016/j.abb.2014.12.013
Rosado MT, Duarte ML, Fausto R (1998) Vibrational spectra of acid and alkaline glycine salts. Vibrat Spec 16(1):35–54. https://doi.org/10.1016/S0924-2031(97)00050-7
Rozencweig M, Von Hoff DD, Slavik M, Muggia FM (1977) Cis-diamminedichloroplatinum(II): a new anticancer drug. Ann Intern Med 86(6):803–812. https://doi.org/10.7326/0003-4819-86-6-803
Safa Shams Abyaneh F, Eslami Moghadam M, Hossaini Sadr M, Divsalar A (2018) Effect of lipophilicity of amylamine and amylglycine ligands on biological activity of new anticancer cisplatin analog. J Biomol Struct Dyn 36(4):893–905. https://doi.org/10.1080/07391102.2017.1301273
Sirajuddin M, Ali S, Badshah A (2013) Drug–DNA interactions and their study by UV–Visible, fluorescence spectroscopies and cyclic voltametry. J Photochem Photobiol B 124:1–19. https://doi.org/10.1016/j.jphotobiol.2013.03.013
Wani TA, Alsaif N, Bakheit AH, Zargar S, Al-Mehizia AA, Khan AA (2020) Interaction of an abiraterone with calf thymus DNA: investigation with spectroscopic technique and modelling studies. Bioorg Chem 100:103957. https://doi.org/10.1016/j.bioorg.2020.103957
Wilson JJ, Lippard SJ (2014) Synthetic methods for the preparation of platinum anticancer complexes. Chem Rev 114(8):4470–4495. https://doi.org/10.1021/cr4004314
Wiltshaw E (1979) Cisplatin in the treatment of cancer. Platin Met Rev 23(3):90–98
Xu ZH, Chen FJ, Xi PX, Liu XH, Zeng ZZ (2008) Synthesis, characterization, and DNA-binding properties of the cobalt(II) and nickel(II) complexes with salicylaldehyde 2-phenylquinoline-4-carboylhydrazone. J Photochem Photobiol A 196(1):77–83. https://doi.org/10.1016/j.jphotochem.2007.11.017
Yadav S, Yousuf I, Usman M, Ahmad M, Arjmand F, Tabassum S (2015) Synthesis and spectroscopic characterization of diorganotin(IV) complexes of N′-(4-hydroxypent-3-en-2-ylidene) isonicotinohydrazide: chemotherapeutic potential validation by in vitro interaction studies with DNA/HSA, DFT, molecular docking and cytotoxic activity. RSC Adv 5(63):50673–50690. https://doi.org/10.1039/C5RA06953J
Yadav P, Yadav JK, Agarwal A, Awasthi SK (2019) Insights into the interaction of potent antimicrobial chalcone triazole analogs with human serum albumin: spectroscopy and molecular docking approaches. RSC Adv 9(55):31969–31978. https://doi.org/10.1039/C9RA04192C
Zhao N, Yan L, Zhao X, Chen X, Li A, Zheng D, Zhou X, Dai X, Xu FJ (2018) Versatile types of organic/inorganic nanohybrids: from strategic design to biomedical applications. Chem Rev 119(3):1666–1762. https://doi.org/10.1021/acs.chemrev.8b00401
Acknowledgements
The authors gratefully thank the financial support of this project by the Ferdowsi University of Mashhad, Mashhad, Iran (Grant No. 48899/3) and the Chemistry & Chemical Engineering Research Center of Iran.
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In memory of our colleague, mentor, and friend, Professor Hossein Eshtiagh-Hosseini (1947–2021) whose friendship will always remain in our hearts and his advice forever in our minds.
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Hosseini˗Hashemi, Z., Mirzaei, M. & Eslami Moghadam , M. Property evaluation of two anticancer candidate platinum complexes with N-isobutyl glycine ligand against human colon cancer. Biometals 35, 987–1009 (2022). https://doi.org/10.1007/s10534-022-00418-0
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DOI: https://doi.org/10.1007/s10534-022-00418-0