Biologically active acylthioureas and their Ni(II) and Cu(II) Complexes: Structural, spectroscopic, anti-proliferative, nucleolytic and antimicrobial studies

Ebube E. Oyeka; Ilknur Babahan; Bernard Eboma; Kenechukwu J. Ifeanyieze; Obinna C. Okpareke; Esin P. Coban; Ali Özmen; Burak Coban; Mehran Aksel; Namık Özdemir; Tatiana V. Groutso; Jude I. Ayogu; Ufuk Yildiz; Mehmet Dinçer Bilgin; H. Halil Biyik; Briana R. Schrage; Christopher J. Ziegler; Jonnie N. Asegbeloyin

doi:10.1016/j.ica.2021.120590

Biologically active acylthioureas and their Ni(II) and Cu(II) Complexes: Structural, spectroscopic, anti-proliferative, nucleolytic and antimicrobial studies

Ebube E. Oyeka, Ilknur Babahan, Bernard Eboma, Kenechukwu J. Ifeanyieze, Obinna C. Okpareke, Esin P. Coban, Ali Özmen, Burak Coban, Mehran Aksel, Namık Özdemir, Tatiana V. Groutso, Jude I. Ayogu, Ufuk Yildiz, Mehmet Dinçer Bilgin, H. Halil Biyik, Briana R. Schrage, Christopher J. Ziegler, Jonnie N. Asegbeloyin

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

The study investigated the effects of morpholine substituent and metal complexation on in vitro anticancer and antimicrobial activities of acylthioureas using two acylthiourea molecules that differ only by the presence of morpholine oxygen; N,N-diethyl-N′-(4-chlorobenzoyl)thiourea (CBDEA) and N-morpholine-N′-(4-chlorobenzoyl)thiourea (CBMOR), and their Ni(II) and Cu(II) complexes (NiCBDEA, CuCBDEA, NiCBMOR, CuCBMOR). All compounds were synthesized and characterized by physicochemical and spectroscopic studies. CBDEA, CuCBDEA, NiCBDEA, CBMOR, and NiCBMOR were structurally elucidated by single-crystal X-ray diffraction. The metal complexes were isolated as neutral four coordinate complexes of the form, ML₂ (M: Ni(II), Cu(II), H.L.: CBDEA/CBMOR) in square-planar geometry. The compounds were screened for DNA binding/cleavage, antimicrobial activity, and anti-proliferative effects on human prostate cancer PC-3 and breast cancer MCF-7 cells. DNA binding interaction studies suggest that the metal complexes bind more strongly to the DNA compared to the ligands. The morpholine derivative CBMOR shows similar activity to CBDEA against PC-3 cell lines but twice as effective against MCF-3 cells at cell death and apoptotic levels. Anticancer activities were enhanced by complexation with Cu(II), as evident in CuCBMOR, which showed the optimal anticancer activity (IC50: 1.76 µM for MCF-7 and 1.97 µM for PC-3), comparable to known anticancer drug paclitaxel. The CuCBMOR apoptosis results show that the cancer cells die by apoptotic mechanisms (Apoptosis rate: 91.53 % in MCF-7 and 85.95 % in PC-3). In vitro screening of the compounds against seventeen bacteria and four yeast strains confirmed antimicrobial potency against more susceptible Gram-positive bacteria strains. The results of the study suggest that some of the compounds could be developed into novel antimicrobial and anticancer agents.

Original language	English
Article number	120590
Journal	Inorganica Chimica Acta
Volume	528
DOIs	https://doi.org/10.1016/j.ica.2021.120590
State	Published - Dec 1 2021
Externally published	Yes

Funding

The authors are grateful to the Department of Chemistry, Akron University , for assistance with X-ray crystal structure determination of CBDEA and CBMOR, School of Chemical Sciences, University of Auckland, New Zealand for crystal data of NiCBDEA and CuCBDEA and Scientific Research Projects Unit of Ondokuz Mayıs University (Project No: PYO.FEN.1906.19.001), Turkey for NiCBMOR. Many thanks to National Centre for Energy Research and Development, University of Nigeria,Nsukka for infrastructural support.

Funders	Funder number
CuCBDEA and Scientific Research Projects Unit of Ondokuz Mayıs University	PYO.FEN.1906.19.001
University of Akron
Department of Chemistry, University of York
University of Auckland

Keywords

Anticancer
Antimicrobial
Breast cancer (MCF-7)
Complexes
DNA binding
Morpholine
Prostate cancer (PC-3)
Thiourea
X-ray diffraction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ica.2021.120590

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Oyeka, E. E., Babahan, I., Eboma, B., Ifeanyieze, K. J., Okpareke, O. C., Coban, E. P., Özmen, A., Coban, B., Aksel, M., Özdemir, N., Groutso, T. V., Ayogu, J. I., Yildiz, U., Dinçer Bilgin, M., Halil Biyik, H., Schrage, B. R., Ziegler, C. J., & Asegbeloyin, J. N. (2021). Biologically active acylthioureas and their Ni(II) and Cu(II) Complexes: Structural, spectroscopic, anti-proliferative, nucleolytic and antimicrobial studies. Inorganica Chimica Acta, 528, Article 120590. https://doi.org/10.1016/j.ica.2021.120590

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title = "Biologically active acylthioureas and their Ni(II) and Cu(II) Complexes: Structural, spectroscopic, anti-proliferative, nucleolytic and antimicrobial studies",

abstract = "The study investigated the effects of morpholine substituent and metal complexation on in vitro anticancer and antimicrobial activities of acylthioureas using two acylthiourea molecules that differ only by the presence of morpholine oxygen; N,N-diethyl-N′-(4-chlorobenzoyl)thiourea (CBDEA) and N-morpholine-N′-(4-chlorobenzoyl)thiourea (CBMOR), and their Ni(II) and Cu(II) complexes (NiCBDEA, CuCBDEA, NiCBMOR, CuCBMOR). All compounds were synthesized and characterized by physicochemical and spectroscopic studies. CBDEA, CuCBDEA, NiCBDEA, CBMOR, and NiCBMOR were structurally elucidated by single-crystal X-ray diffraction. The metal complexes were isolated as neutral four coordinate complexes of the form, ML2 (M: Ni(II), Cu(II), H.L.: CBDEA/CBMOR) in square-planar geometry. The compounds were screened for DNA binding/cleavage, antimicrobial activity, and anti-proliferative effects on human prostate cancer PC-3 and breast cancer MCF-7 cells. DNA binding interaction studies suggest that the metal complexes bind more strongly to the DNA compared to the ligands. The morpholine derivative CBMOR shows similar activity to CBDEA against PC-3 cell lines but twice as effective against MCF-3 cells at cell death and apoptotic levels. Anticancer activities were enhanced by complexation with Cu(II), as evident in CuCBMOR, which showed the optimal anticancer activity (IC50: 1.76 µM for MCF-7 and 1.97 µM for PC-3), comparable to known anticancer drug paclitaxel. The CuCBMOR apoptosis results show that the cancer cells die by apoptotic mechanisms (Apoptosis rate: 91.53 % in MCF-7 and 85.95 % in PC-3). In vitro screening of the compounds against seventeen bacteria and four yeast strains confirmed antimicrobial potency against more susceptible Gram-positive bacteria strains. The results of the study suggest that some of the compounds could be developed into novel antimicrobial and anticancer agents.",

keywords = "Anticancer, Antimicrobial, Breast cancer (MCF-7), Complexes, DNA binding, Morpholine, Prostate cancer (PC-3), Thiourea, X-ray diffraction",

author = "Oyeka, {Ebube E.} and Ilknur Babahan and Bernard Eboma and Ifeanyieze, {Kenechukwu J.} and Okpareke, {Obinna C.} and Coban, {Esin P.} and Ali {\"O}zmen and Burak Coban and Mehran Aksel and Namık {\"O}zdemir and Groutso, {Tatiana V.} and Ayogu, {Jude I.} and Ufuk Yildiz and {Din{\c c}er Bilgin}, Mehmet and {Halil Biyik}, H. and Schrage, {Briana R.} and Ziegler, {Christopher J.} and Asegbeloyin, {Jonnie N.}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",

year = "2021",

month = dec,

day = "1",

doi = "10.1016/j.ica.2021.120590",

language = "English",

volume = "528",

journal = "Inorganica Chimica Acta",

issn = "0020-1693",

publisher = "Elsevier",

}

Oyeka, EE, Babahan, I, Eboma, B, Ifeanyieze, KJ, Okpareke, OC, Coban, EP, Özmen, A, Coban, B, Aksel, M, Özdemir, N, Groutso, TV, Ayogu, JI, Yildiz, U, Dinçer Bilgin, M, Halil Biyik, H, Schrage, BR, Ziegler, CJ & Asegbeloyin, JN 2021, 'Biologically active acylthioureas and their Ni(II) and Cu(II) Complexes: Structural, spectroscopic, anti-proliferative, nucleolytic and antimicrobial studies', Inorganica Chimica Acta, vol. 528, 120590. https://doi.org/10.1016/j.ica.2021.120590

TY - JOUR

T1 - Biologically active acylthioureas and their Ni(II) and Cu(II) Complexes

T2 - Structural, spectroscopic, anti-proliferative, nucleolytic and antimicrobial studies

AU - Oyeka, Ebube E.

AU - Babahan, Ilknur

AU - Eboma, Bernard

AU - Ifeanyieze, Kenechukwu J.

AU - Okpareke, Obinna C.

AU - Coban, Esin P.

AU - Özmen, Ali

AU - Coban, Burak

AU - Aksel, Mehran

AU - Özdemir, Namık

AU - Groutso, Tatiana V.

AU - Ayogu, Jude I.

AU - Yildiz, Ufuk

AU - Dinçer Bilgin, Mehmet

AU - Halil Biyik, H.

AU - Schrage, Briana R.

AU - Ziegler, Christopher J.

AU - Asegbeloyin, Jonnie N.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - The study investigated the effects of morpholine substituent and metal complexation on in vitro anticancer and antimicrobial activities of acylthioureas using two acylthiourea molecules that differ only by the presence of morpholine oxygen; N,N-diethyl-N′-(4-chlorobenzoyl)thiourea (CBDEA) and N-morpholine-N′-(4-chlorobenzoyl)thiourea (CBMOR), and their Ni(II) and Cu(II) complexes (NiCBDEA, CuCBDEA, NiCBMOR, CuCBMOR). All compounds were synthesized and characterized by physicochemical and spectroscopic studies. CBDEA, CuCBDEA, NiCBDEA, CBMOR, and NiCBMOR were structurally elucidated by single-crystal X-ray diffraction. The metal complexes were isolated as neutral four coordinate complexes of the form, ML2 (M: Ni(II), Cu(II), H.L.: CBDEA/CBMOR) in square-planar geometry. The compounds were screened for DNA binding/cleavage, antimicrobial activity, and anti-proliferative effects on human prostate cancer PC-3 and breast cancer MCF-7 cells. DNA binding interaction studies suggest that the metal complexes bind more strongly to the DNA compared to the ligands. The morpholine derivative CBMOR shows similar activity to CBDEA against PC-3 cell lines but twice as effective against MCF-3 cells at cell death and apoptotic levels. Anticancer activities were enhanced by complexation with Cu(II), as evident in CuCBMOR, which showed the optimal anticancer activity (IC50: 1.76 µM for MCF-7 and 1.97 µM for PC-3), comparable to known anticancer drug paclitaxel. The CuCBMOR apoptosis results show that the cancer cells die by apoptotic mechanisms (Apoptosis rate: 91.53 % in MCF-7 and 85.95 % in PC-3). In vitro screening of the compounds against seventeen bacteria and four yeast strains confirmed antimicrobial potency against more susceptible Gram-positive bacteria strains. The results of the study suggest that some of the compounds could be developed into novel antimicrobial and anticancer agents.

AB - The study investigated the effects of morpholine substituent and metal complexation on in vitro anticancer and antimicrobial activities of acylthioureas using two acylthiourea molecules that differ only by the presence of morpholine oxygen; N,N-diethyl-N′-(4-chlorobenzoyl)thiourea (CBDEA) and N-morpholine-N′-(4-chlorobenzoyl)thiourea (CBMOR), and their Ni(II) and Cu(II) complexes (NiCBDEA, CuCBDEA, NiCBMOR, CuCBMOR). All compounds were synthesized and characterized by physicochemical and spectroscopic studies. CBDEA, CuCBDEA, NiCBDEA, CBMOR, and NiCBMOR were structurally elucidated by single-crystal X-ray diffraction. The metal complexes were isolated as neutral four coordinate complexes of the form, ML2 (M: Ni(II), Cu(II), H.L.: CBDEA/CBMOR) in square-planar geometry. The compounds were screened for DNA binding/cleavage, antimicrobial activity, and anti-proliferative effects on human prostate cancer PC-3 and breast cancer MCF-7 cells. DNA binding interaction studies suggest that the metal complexes bind more strongly to the DNA compared to the ligands. The morpholine derivative CBMOR shows similar activity to CBDEA against PC-3 cell lines but twice as effective against MCF-3 cells at cell death and apoptotic levels. Anticancer activities were enhanced by complexation with Cu(II), as evident in CuCBMOR, which showed the optimal anticancer activity (IC50: 1.76 µM for MCF-7 and 1.97 µM for PC-3), comparable to known anticancer drug paclitaxel. The CuCBMOR apoptosis results show that the cancer cells die by apoptotic mechanisms (Apoptosis rate: 91.53 % in MCF-7 and 85.95 % in PC-3). In vitro screening of the compounds against seventeen bacteria and four yeast strains confirmed antimicrobial potency against more susceptible Gram-positive bacteria strains. The results of the study suggest that some of the compounds could be developed into novel antimicrobial and anticancer agents.

KW - Anticancer

KW - Antimicrobial

KW - Breast cancer (MCF-7)

KW - Complexes

KW - DNA binding

KW - Morpholine

KW - Prostate cancer (PC-3)

KW - Thiourea

KW - X-ray diffraction

UR - http://www.scopus.com/inward/record.url?scp=85114469875&partnerID=8YFLogxK

U2 - 10.1016/j.ica.2021.120590

DO - 10.1016/j.ica.2021.120590

M3 - Article

AN - SCOPUS:85114469875

SN - 0020-1693

VL - 528

JO - Inorganica Chimica Acta

JF - Inorganica Chimica Acta

M1 - 120590

ER -

Biologically active acylthioureas and their Ni(II) and Cu(II) Complexes: Structural, spectroscopic, anti-proliferative, nucleolytic and antimicrobial studies

Abstract

Funding

Keywords

UN SDGs

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