Synthesis of Chlorotoxin by Native Chemical Ligation

Abstract

A series of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) metal complexes are derived from ligand (N-(3-methoxyphenyl)-2-[(2E)-3-phenylprop-2-enoyl]hydrazinecarboxamide[MPH], and structurally characterized by various physicochemical and spectral tools such as IR, UV-Visible, 1H-NMR, LC-Mass, powder XRD and TGA-DTC.These studies showed that the ligand coordinated to the metal atom in a bidentate manner and have octahedral environment.X-ray diffraction studies indicates that the Co(II) and Cu(II) complexes are Crystalline in nature, Degradation mechanism, kinetic and thermodynamic parameters of the synthesized metal complexes has been evaluated.The synthesized compounds were evaluated for in vitroantioxidant DPPH assay, in which metal complexes showed excellent activity. The molecular docking analysis by using human antioxidant enzyme DTT (PDB: 3MNG)have also been evaluated. The ligand and their metal complexes were screened for their antifungal and antibacterial activities against different species of pathogenic fungi and bacteria.

Keywords

• Semicarbazide
• Metal complexes. Powder XRD
• TGA
• antioxidant

References

1. 1. Asghar SF, Yasin KA, Habib-ur-Rehman, Aziz S. Synthesis and cyclisation of 1,4-disubstituted semicarbazides. Natural Product Research. 2010 Mar 10;24(4):315–25
2. 2. Rajesh-Rane A, Shital-Naphade S, Pavan Kumar, Mahesh Palkar B, Mahamadhanif Shaikh S, Rajshekhar Karpoormath. Synthesis of novel 4-nitropyrrole-based semicarbazide and thiosemicarbazide hybrids with antimicrobial and anti-tubercular activity. Bioorganic & Medicinal Chemistry Letters. 2014 Jul 24; 10: 3079-3083.
3. 3. Pituchaa M, Karczmarzykb Z, Kosikowska U, and Malm A. Synthesis, Experimental and Theoretical Study on the Structure of Some Semicarbazides with Potential Antibacterial Activity. Zeitschriftfür Naturforschung B. 2011 Apr 66;(5) 971-87
4. 4. Rafat-Mohareb M. and Abeer Mohamed A. Uses of 1-Cyanoacetyl-4-Phenyl-3-Thiosemicarbazide in the Synthesis of Antimicrobial and Antifungal Heterocyclic Compounds. International Research Journal of Pure & Applied Chemistry. 2012 Jul 2(2): 2012 144-155,
5. 5. Gursoy A, Terzioglu N, Otuk G. Synthesis of some new hydrazide-hydrazones, thiosemicarbazides and thiazolidinones as possible antimicrobials. European Journal of Medicinal Chemistry. 1997 Jun 32(9):753-757.
6. 6. Narang KK, Singh VP. Synthesis and characterization of cobalt (II), nickel (II), copper (II) and zinc (II) complexes with acetylacetone bis-benzoyl hydrazone and acetylacetone bis isonicotinoyl hydrazone. Transition Metal Chemistry. 1993 Dec 10(18): 287-290.
7. 7. El-Azab AS, El-Tahir KEH. Synthesis and anticonvulsant evaluation of some new 2,3,8-trisubstituted-4(3H)-quinazoline derivatives. Bioorganic & Medicinal Chemistry Letters, 2012 Oct 22(1): 327-333.
8. 8. Aly MM, Mohamed YA, El-Bayouki KAM, Basyouni WM, Abbas SY. Synthesis of some new 4(3H)-quinazolinone-2-carboxaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities. European Journal of Medicinal Chemistry, 2010 Apr 45(8): 3365- 3373.

9. 9. Azam F, Alkskas IA, Khokra SL, Prakash O. Synthesis of some novel N 4 - (naphtha[1,2-d]thiazol-2-yl) semicarbazides as potential anticonvulsants. European Journal of Medicinal Chemistry. 2009 Nov 44(1): 203-211.
10. 10. Shashikumar ND, Krishnamurthy G, Bhojya-Naik HS, Lokesh MR, Jithendra-kumara KS. Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies. Journal of chemical sciences. 2014 Jan 126(1): 205–212.
11. 11. Manjuraj T, Krishnamurthy G, Yadav D. Bodke, BhojyaNaik H.S, Metal complexes of quinolin-8-yl [(5-methoxy-1H-benzimidazol-2-yl)sulfanyl]acetate: Spectral, XRD, thermal, cytotoxic, molecular docking and biological evaluation. Journal of Molecular Structure, Volume 1148, (15): 2017; 231–237.
12. 12. Nakamoto K, Infrared and Raman Spectra of Inorganic and Coordination Compounds. In:Chalmers JM, Griffiths PR, editors. Handbook of vibrational spectroscopy, Chichester, UK: John Wiley & Sons, Ltd; 2006.
13. 13. Sangeetha Gowda KR, Bhojya-Naik HS, Vinay-Kumar B, Sudhamani CN, Sudeep HV, Ravikumar-Naik TR, Krishnamurthy G. Synthesis, antimicrobial, DNA-binding and photonuclease studies of Cobalt(III) and Nickel(II) Schiff base complexes. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2013 Jun 105(10): 229–237.
14. 14. Emelda AR, Jayachandramani N, Ravichandran S. Synthesis, Characterization and Antimicrobial Study of a New Mannich Base, N-(1-Piperidinobenzyl)benzamide and its Transition Metal(II) Complexes. Asian Journal of Chemistry. 2008 Feb 2(20): 2485-2490.
15. 15. Ashraf A, Siddiqui WA, Akbar J, Mustafa G, Krautscheid H, Ullah N. Metal complexes of benzimidazole derived sulfonamide: Synthesis, molecular structures and antimicrobial activity. Inorganic Chimca Acta. 2016 Mar (443): 179–85.
16. 16. Lever A.B.P. Inorganic electronic spectroscopy. 2nd ed. Amsterdam ; New York: Elsevier; 1984 863.
17. 17. El-Gammal OA, Mostafa MM. Synthesis, characterization, molecular modeling and antioxidant activity of Girard′s T thiosemicarbazide and its complexes with some transition metal ions SpectrochimicaActa Part A: Molecular and Biomolecular Spectroscopy,2014 Mar(127): 530–42.
18. 18. Rahaman F, Mruthyunjayaswamy BHM. Synthesis, spectral characterization and biological activity studies of transition metal complexes of Schiff base ligand containing indole moiety. Complex Metals. (31): (2014); 88–95.
19. 19. Bal M, CEYHAN G, AVAR B, KÖSE M, Kayraldiz A, KURTOĞLU M. Synthesis and X-ray powder diffraction, electrochemical, and genotoxic properties of a new azo-Schiff base and its metal complexes. Turkish journal of chemistry. 2014 Apr 17;38(2):222-41.
20. 20. Joseph J, Mehta HB. Synthesis, characterization, and thermal analysis of transition metal complexes of polydentate ONO donor Schiff base ligand. Russian Journal of Coordination Chemistry. 2007 Mar 12(33): 124-129.
21. 21. Donia A. M, Al-Ansi T. Y and Othman M. Q., Journal of Thermal Analysis. (50) 1997 857.
22. 22. Venugopala Reddy KR, Keshavayya J, Seetharamappa J. Synthesis, spectral, magnetic and thermal studies on symmetrically substituted metal (II) 1,3,8,10,15,17,22,24-octachloro phthalocyanines, Dyes Pigments, 2003 Nov (59):237-244.
23. 23. Yapati H, Devineni S.R, Chirumamilla S, Kalluru S. Synthesis, characterization and studies on antioxidant and molecular docking of metal complexes of 1-(benzo[d]thiazol-2-yl)thiourea. Journal of Chemical Sciences. 2016 Jan (128): 43–51.
24. 24. Harinath Y, Subbarao D, Suresh C, Seshaiah K. Synthesis, characterization and studies on antioxidant and molecular docking of metal complexes of 1-(benzo[d]thiazol-2-yl)thiourea. Journal of Chemical Sciences. 2016 Jan 128(1): 43-51.
25. 25. Hall Parsonage D, Poole LB, Karplus PA. Structural evidence that peroxiredoxin catalytic power is based on transition-state stabilization. Journal of Molecular Biology. 2010 10; 402(1)194-209.
26. 26. Abdel Nasser MA, Alaghaz-Badr A, El-Sayed A, Ahmed, El-Henawy, Reda, Ammar AA. Synthesis, spectroscopic characterization, potentiometric studies, cytotoxic studies and molecular docking studies of DNA binding of transition metal complexes with 1,1-diaminopropane–Schiff base. Journal of Molecular Structure, 2013 Dec 1035(12): 83–93.
27. 27. Mohammed Shafeeulla R, Ganganaik Krishnamurthy, Halehatti S. Bhojynaik, Manjuraj T. Synthesis, Cytotoxicity, and Molecular Docking Study of Complexes Containing Thiazole Moiety. JOTCSA. 2017 Aug 4(3): 787-810.
28. 28. Bhimagouda-Patil S, Krishnamurthy G, Bhojya-Naik HS, Prashant R. Latthe, Manjunath-Ghate. Synthesis, characterization and antimicrobial studies of 2-(4-methoxy-phenyl)-5-methyl-4-(2-arylsulfanyl-ethyl)-2,4-dihydro-[1,2,4] triazolo-3-ones and their corresponding sulfones. European Journal of Medicinal Chemistry 12(45): 3329-3334.
29. 29. Jayamani A, Sengottuvelan N, Chakkaravarthi G, Synthesis, structural, electrochemical, DNA interaction, antimicrobial and molecular docking studies on dimeric copper(II) complexes involving some potential bidentate ligands. Polyhedron 2014 Feb 81(12): 764–76.