SYNTHESIS, CHARACTERIZATION AND PHARMACOLOGICAL STUDIES OF METAL(II) COMPLEXES WITH HIGHLY CONJUGATIVE HETEROCYCLIC LIGANDS
Main Article Content
Keywords
Complexes, catalytic, copper enzymes, intercalation, mimetic
Abstract
A novel bioactive metal(II) complexes with the molecular formulae of [MIIL] (where M= Cu(II), Ni(II), Co(II) and Zn(II); L = heterocyclic ligand, curcumin derivative) were synthesized. They were characterized using elemental, thermal analysis, molar conductance, cyclic voltammetry, magnetic moment measurements as well spectral (FT-IR, UV–Vis and ESR) techniques. Powder X-ray diffraction spectral data has been utilized for the study of crystalline properties of metal complexes. The DNA interaction study performed by UV–visible spectroscopy as well as by molecular docking suggests the tested compounds interact with DNA through intercalation mode. The oral glucose tolerance test was used for the hypoglycemic test, and the phenobarbitone-induced sleeping duration test was used to evaluate the CNS depressant activity of metal Schiff base complexes
References
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25. Alam MA, Al-Jenoobi FI, Al-mohizea AM (2011) Everted gut sac model as a tool in pharmaceutical research: limitations and applications. J Pharm Pharmacol 64:326–336
26. Mondal P, Bose A (2019) Spectroscopic overview of quercetin and its Cu (II) complex interaction with serum albumins. Bioimpacts 9(2):115–121. https://doi.org/10.15171/bi.2019.15
27. Kalinowska M, Świderski G, Matejczyk M, Lewandowski W (2016) Spectroscopic, thermogravimetric and biological studies of Na(I), Ni(II) and Zn(II) complexes of quercetin. J Therm Anal Calorim 126(1):141–148. https://doi.org/10.1007/s10973-016-5362-5
28. Dehghan G, Khoshkam Z (2012) Tin (II)-quercetin complex: synthesis, spectral characterization and antioxidant activity. Food Chem 131(2):422–426.
https://doi.org/10.1016/j.foodchem.2011.08.074
29. Wilson TH, Wiseman G (1954) The use of sacs of everted small intestine for the study of the transference of substances from the mucosal to the serosal surface. J Physiol 123:116–125.
30. Challa VR, Ravindra Babu P, Challa SR, Johnson B, Maheswari C (2013) Pharmacokinetic interaction study between quercetin and valsartan in rats and in vitro models. Drug Dev Ind Pharm 39(6):865–872. https://doi.org/10.3109/03639045.2012.693502
31. Adukondalu D, Shravan Kumar Y, Vamshi Vishnu Y, Shiva Kumar R, Madhusudan Rao Y (2010) Effect of pomegranate juice pre-treatment on the transport of carbamazepine across rat intestine. DARU J Pharm Sci 18:254–259
32. Bedada SK, Appani R, Boga PK (2017) Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro, in situ and in vivo evaluation. Drug Dev Ind Pharm 43(6):932–938. https://doi.org/10.1080/03639045.2017.1285310
33. Yumoto R, Murakami T, Nakamoto Y, Hasegawa R, Nagai J, Takano M (1999) Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P-450 3A-related compounds. J Pharmacol Exper Ther 289:149–155
34. Li M, Si L, Pan H, Rabba AK, Yan F, Qiu J, Li G (2011) Excipients enhance intestinal absorption of ganciclovir by P-gp inhibition: assessed in vitro by everted gut sac and in situ by improved intestinal perfusion. Int J Pharm 403(1-2):37–45.
https://doi.org/10.1016/j.ijpharm.2010.10.017
35. Sultana N, Arayne MS, Naveed S (2010) Simultaneous determination of captopril and statins in API, pharmaceutical formulations and in human serum by RP-HPLC. J Chin Chem Soc 57(3A):378–383. https://doi.org/10.1002/jccs.201000056
36. Ruan LP, Chen S, Yu BY, Zhu DN, Cordell GA, Qiu SX (2006) Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. Eur J Med Chem 41(5):605–610. https://doi.org/10.1016/j.ejmech.2006.01.013
2. Smith RD, Mallath MK (2019) History of the growing burden of cancer in India: from antiquity to the 21st century. J Glob Oncol 5:1–15. https://doi.org/10.1200/JGO.19.00048
3. Zheng HC (2017) The molecular mechanisms of chemoresistance in cancers. Oncotarget 8(35):59950–59964. https://doi.org/10.18632/oncotarget.19048
4. Schirrmacher V (2019) From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment (Review). Int J Oncol 54(2):407–419. https://doi.org/10.3892/ijo.2018.4661
5. Wang X, Zhang H, Chen X (2019) Drug resistance and combating drug resistance in cancer. Cancer Drug Resist 2:141–160
6. Salehi B, Machin L, Monzote L, Sharifi-Rad J, Ezzat SM, Salem MA, Merghany RM, El Mahdy NM, Kılıç CS, Sytar O, Sharifi-Rad M, Sharopov F, Martins N, Martorell M, Cho WC (2020) Therapeutic potential of quercetin: new insights and perspectives for human health. ACS Omega 5(20):11849–11872. https://doi.org/10.1021/acsomega.0c01818
7. Lesjak M, Beara I, Simin N, Pintać D, Majkić T, Bekvalac K, Orčić D, Mimica-Dukić N (2018) Antioxidant and anti-inflammatory activities of quercetin and its derivatives. J Funct Foods 40:68–75. https://doi.org/10.1016/j.jff.2017.10.047
8. Xu D, Hu M-J, Wang Y-Q, Cui Y-L (2019) Antioxidant activities of quercetin and its complexes for medicinal application. Molecules 24(6):1123–1138.
https://doi.org/10.3390/molecules24061123
9. Torreggiani A, Tamba M, Trinchero A, Bonora S (2005) Copper (II)–quercetin complexes in aqueous solutions: spectroscopic and kinetic properties. J Mol Struct 744–747:759–766
10. De Castilho TS, Matias TB, Nicolini KP, Nicolini J (2018) Study of interaction between metal ions and quercetin. Food Sci Human Wellness 7(3):215–219.
https://doi.org/10.1016/j.fshw.2018.08.001
11. Liu Y, Guo M (2015) Studies on transition metal-quercetin complexes using electrospray ionization tandem mass spectrometry. Molecules 20(5):8583–8594.
https://doi.org/10.3390/molecules20058583
12. Ahmadi SM, Dehghan G, Hosseinpourfeizi MA, Dolatabadi JE, Kashanian S (2011) Preparation, characterization, and DNA binding studies of water-soluble quercetin--molybdenum(VI) complex. DNA Cell Biol 30(7):517–523.
https://doi.org/10.1089/dna.2010.1205
13. Khater M, Ravishankar D, Greco F, Osborn HMI (2019) Metal complexes of flavonoids: their synthesis, characterization and enhanced antioxidant and anticancer activities. Future Med Chem 11(21):2845–2867. https://doi.org/10.4155/fmc-2019-0237
14. Da Silva WMB, de Oliveira PS, Alves DR, de Morais MS (2020) Synthesis of quercetin-metal complexes, in vitro and in silico anticholinesterase and antioxidant evaluation, and in vivo toxicological and anxiolitic activities. Neurotox Res 37(4):893–903.
https://doi.org/10.1007/s12640-019-00142-7
15. Ulusoy HG, Sanlier N (2020) A minireview of quercetin: from its metabolism to possible mechanisms of its biological activities. Crit Rev Food Sci Nutr 60(19):3290–3303. https://doi.org/10.1080/10408398.2019.1683810
16. Massi A, Bortolini O, Ragno D, Bernardi T, Sacchetti G, Tacchini M, De Risi C (2017) Research progress in the modification of quercetin leading to anticancer agents. Molecules 22(8):1270. https://doi.org/10.3390/molecules22081270
17. Chen X, Wu X, He Z, Zhang J, Cao Y, Mao D, Feng C, Tian B, Chen G (2020) Molecular docking-assisted design and synthesis of an anti-tumor quercetin-Se(IV) complex. New J Chem 44(20):8434–8441. https://doi.org/10.1039/C9NJ06136C
18. Roy S, Banerjee S, Chakraborty T (2018) Vanadium quercetin complex attenuates mammary cancer by regulating the P53, Akt/mTOR pathway and downregulates cellular proliferation correlated with increased apoptotic events. Biometals 31(4):647–671.
https://doi.org/10.1007/s10534-018-0117-3
19. Li S, Zhao Q, Wang B, Yuan S, Wang X, Li K (2018) Quercetin reversed MDR in breast cancer cells through down-regulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation. Phytother Res 32(8):1530–1536.
https://doi.org/10.1002/ptr.6081
20. Zhou Y, Zhang J, Wang K, Han W, Wang X, Gao M, Wang Z, Sun Y, Yan H, Zhang H, Xu X, Yang D-H (2020) Quercetin overcomes colon cancer cells resistance to chemotherapy by inhibiting solute carrier family 1, member 5 transporter. Eur J Pharmacol 881:173185.
https://doi.org/10.1016/j.ejphar.2020.173185
21. Shin SC, Choi JS, Li X (2006) Enhanced bioavailability of tamoxifen after oral administration of tamoxifen with quercetin in rats. Int J Pharm 313(1-2):144–149.
https://doi.org/10.1016/j.ijpharm.2006.01.028
22. Mohana S, Ganesan M, Agilan B, Karthikeyan R, Srithar G, Mary RB, Ananthakrishnan D, Velumurugan D, Rajendraprasad N, Ambudkar SV (2016) Screening dietary flavonoids for the reversal of P-glycoprotein mediated multidrug resistance in cancer. Mol BioSyst 12(8):2458–2470. https://doi.org/10.1039/C6MB00187D
23. Kim MK, Choo H, Chong Y (2014) Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators of P-glycoprotein based multidrug resistance. J Med Chem 57(17):7216–7233. https://doi.org/10.1021/jm500290c
24. Nolan JP, Hare MDDK, McDevitt MDJJ, Ali MVMD (1977) In vitro studies of intestinal endotoxin absorption I. Kinetics of absorption in the isolated everted gut sac. Gastroenterology 72(3):434–439
25. Alam MA, Al-Jenoobi FI, Al-mohizea AM (2011) Everted gut sac model as a tool in pharmaceutical research: limitations and applications. J Pharm Pharmacol 64:326–336
26. Mondal P, Bose A (2019) Spectroscopic overview of quercetin and its Cu (II) complex interaction with serum albumins. Bioimpacts 9(2):115–121. https://doi.org/10.15171/bi.2019.15
27. Kalinowska M, Świderski G, Matejczyk M, Lewandowski W (2016) Spectroscopic, thermogravimetric and biological studies of Na(I), Ni(II) and Zn(II) complexes of quercetin. J Therm Anal Calorim 126(1):141–148. https://doi.org/10.1007/s10973-016-5362-5
28. Dehghan G, Khoshkam Z (2012) Tin (II)-quercetin complex: synthesis, spectral characterization and antioxidant activity. Food Chem 131(2):422–426.
https://doi.org/10.1016/j.foodchem.2011.08.074
29. Wilson TH, Wiseman G (1954) The use of sacs of everted small intestine for the study of the transference of substances from the mucosal to the serosal surface. J Physiol 123:116–125.
30. Challa VR, Ravindra Babu P, Challa SR, Johnson B, Maheswari C (2013) Pharmacokinetic interaction study between quercetin and valsartan in rats and in vitro models. Drug Dev Ind Pharm 39(6):865–872. https://doi.org/10.3109/03639045.2012.693502
31. Adukondalu D, Shravan Kumar Y, Vamshi Vishnu Y, Shiva Kumar R, Madhusudan Rao Y (2010) Effect of pomegranate juice pre-treatment on the transport of carbamazepine across rat intestine. DARU J Pharm Sci 18:254–259
32. Bedada SK, Appani R, Boga PK (2017) Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro, in situ and in vivo evaluation. Drug Dev Ind Pharm 43(6):932–938. https://doi.org/10.1080/03639045.2017.1285310
33. Yumoto R, Murakami T, Nakamoto Y, Hasegawa R, Nagai J, Takano M (1999) Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P-450 3A-related compounds. J Pharmacol Exper Ther 289:149–155
34. Li M, Si L, Pan H, Rabba AK, Yan F, Qiu J, Li G (2011) Excipients enhance intestinal absorption of ganciclovir by P-gp inhibition: assessed in vitro by everted gut sac and in situ by improved intestinal perfusion. Int J Pharm 403(1-2):37–45.
https://doi.org/10.1016/j.ijpharm.2010.10.017
35. Sultana N, Arayne MS, Naveed S (2010) Simultaneous determination of captopril and statins in API, pharmaceutical formulations and in human serum by RP-HPLC. J Chin Chem Soc 57(3A):378–383. https://doi.org/10.1002/jccs.201000056
36. Ruan LP, Chen S, Yu BY, Zhu DN, Cordell GA, Qiu SX (2006) Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. Eur J Med Chem 41(5):605–610. https://doi.org/10.1016/j.ejmech.2006.01.013
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Jan 16, 2022
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B. Bincy, Joseph, & E.H. Edinsha Gladis. (2022). SYNTHESIS, CHARACTERIZATION AND PHARMACOLOGICAL STUDIES OF METAL(II) COMPLEXES WITH HIGHLY CONJUGATIVE HETEROCYCLIC LIGANDS. Journal of Population Therapeutics and Clinical Pharmacology, 29(01), 243–260. https://doi.org/10.53555/jptcp.v29i01.3851
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Author Biographies
B. Bincy, Joseph
Dept. of Chemistry, Noorul Islam Centre for Higher Education, Kumaracoil-629180, Tamilnadu
Mob: 91-8610748179
E.H. Edinsha Gladis
Dept. of Chemistry, Noorul Islam Centre for Higher Education, Kumaracoil-629180, Tamilnadu