Illustration for series of new metal ion complexes extracted from pyrazolone derivative, spectral, thermal, QSAR, DFT/B3LYP, docking and antitumor investigations Fawaz A. Saad a , Nashwa M. El-Metwaly a,b, ⁎, Thoraya A. Farghaly a,c , Marwa G. Elghalban a,b , Reem K. Shah a , Gamil A. Al-Hazmi d,e , Karmel A. Saleh f , Mohammad Y. Alfaifi f a Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukkarramah, Saudi Arabia b Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt c Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt d Chemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, Saudi Arabia e Chemistry Department, Faculty of Applied Sciences, Taiz University, P.O. Box 82, Taiz, Yemen f Biology Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, Saudi Arabia abstract article info Article history: Received 29 October 2016 Received in revised form 7 November 2016 Accepted 9 November 2016 Available online 21 November 2016 New VO(II), Mn(II), Co(II), Ni(II) and Cu(II) - pyrazolone complexes were isolated and deliberately characterized. The analytical and spectral tools emphasis on the isolation of bi-nuclear complexes except Mn(II) one. Spectral parameters and reduced magnetic moments are the bases for proposing bi-nuclear complexes. Variable coordi- nation nos. are observed with isolated complexes in-between four, five or six coordination around central atoms. TG analysis and kinetic parameters are concerned in study to examine the thermal stability of complexes. Implementing Gaussian09 program to optimize the structural formula for the investigated compounds. Applying DFT/B3LYP method, the frontier energy gapes were calculated and other important theoretical parameters. QSAR calculations proposes a distinguish biological activity for pyrazolone ligand. Molecular docking using Auto Dock tools were utilized to explain the experimental behavior of the organic compound towards the microorganisms through theoretical visualization. The docked complexes of 2YXS, 2CGY and 2JW2 protein receptors for prostate, colon and liver carcinoma were investigated and the complexation energies were calculated. The estimated en- ergies display best expectation for excellence antitumor activity for pyrazolone compound towards variable car- cinoma. IC 50 calculated represent an excellent priority for Cu(II) complex in overcoming liver and prostate carcinoma cell lines in comparing with reference drug. Moreover, the Mn(II) complex displays high comparative impact also with colon carcinoma. © 2016 Elsevier B.V. All rights reserved. Keywords: DFT/B3LYP Molecular docking Spectral Tem Antitumor 1. Introduction Pyrazolone compounds refer to class of 5-membered ring structures include two nitrogen atoms and one carbonyl group. Their chemistry is significantly interesting because their extensive applications in thera- peutic field [1–3] and anti-inflammatory [4,5]. The coordination chem- istry will be enriched with the use of such important compound. The former studies introduces Zn(II) and Hg(II) metal ion complexes de- rived from pyrazolone derivatives with potential antitumor activity [6]. Also, in agriculture, they are used as pesticides [7]. Pyrazoles are po- tential appreciate to form complexes, they are suitable agents for inves- tigating active sites of bio-molecules [8] and for modeling bio-systems for oxygen transfer [9]. Metal ions are usually bonded to the imidazole moiety of hystidine, which is a part of proteins in living organisms. From the literature reports [10], both of pyrazole and imidazole are proper to mimic enzymatic reactions. The coordination chemistry of oxovanadium and copper ions are highly concerned because of their im- portant role in biological and catalytic systems [11–13]. This is due to their electronic configuration are easily specified by EPR study. The aim of this work is to use new pyrazolone derivative includes multi- donor centers to give a great chance for poly-nuclear complexes. Such poly-nuclear complexes may serve excellently in the biological field based on the intensive effect of the metallic role and pyrazolone ring. So, the preparation of poly-nuclear complexes serves as antitumor agent is the main goal in our study. Intensive spectral and computation- al studies will be concerned. Gaussian09 molecular modeling, QSAR and Autodock tools are the computational tools implemented. Antitumor activity will be carried out against three carcinoma cell lines to give a Journal of Molecular Liquids 229 (2017) 614–627 ⁎ Corresponding author at: Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukkarramah, Saudi Arabia. E-mail address: n_elmetwaly00@yahoo.com (N.M. El-Metwaly). http://dx.doi.org/10.1016/j.molliq.2016.11.035 0167-7322/© 2016 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq