F. Alminderej, A. Lotfi
Mar 23, 2021
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The Egyptian Journal of Chemistry
Abstract
Two Schiff base ligands ((benzimidazol-2-phenyl)iminomethyl)phenol (HL1) (1) and 2-(1-H-benzimidazol-2yl)phenyl)imino)methyl) naphthol (HL2) (2) were synthesized via condensation of 2-(1H-benzimizadol-2-yl)aniline and respectively salicylaldehyde or naphtylaldehyde. The synthesis of mixed complexes (3)-(6) was realized by reacting ligands HL1 (1) and HL2 (2), copper salt (CuCl2.2H2O) and respectively one equivalent of 2-mercaptobenzothiazole or 2aminobenzothiazole. The ligands as well as the metal complexes have been identified with multiple spectroscopic techniques. The results data indicate that the copper is linked to ligands via deprotonated phenolic oxygen atom, nitrogen or sulphur atom of co-ligands and the coordination was realized through the azomethine group. X-ray powder diffraction analysis of complexes suggests that they posses monoclinic structure for complexes (3) and (4), while complex (5) has orthorhombic structure and rhombohedral structure for complex (6). The in vitro anticancer activities of the different complexes were evaluated and the results revealed an important cytotoxicity of complex (6) against lung human cancer A-549 and very good selectivity with 12.4 values of inhibitory concentration IC 50. The best result was described with complex (4) and present high activities on both A-549 and Caco-2 indicating good selectivity on lung human cancer A-549 and moderate selectivity on colorectal cell line Caco-2 with 10.9 and 15.7 respectively of IC 50. Keys words: Copper mixed complex, Schiff base, anticancer evaluation, 2-(1H-Benzimizadol-2-yl) aniline, 2aminobenzothiazole, 2-mercaptobenzothiazole Introduction Benzimidazole scaffolds is an excellent structure that displays great physiological and therapeutic activity. In past years, the study reporting the influence of systems containing benzimidazole moiety was considerably increased and incorporated vast activities including antimicrobial [1,2], antihelminthic [3], antithrombotic, antiplatelet and anticoagulant [4], anti-inflammatory [5,6], antiulcer [7], antifungal and acetylcholinesterase [8], antiprotozoal and antitubercular [9], antileishmanial [10], antimycobacterial [11], antiviral [12], anti-HIV [13] and antitumour [14]. In addition, benzimidazole target was described as inhibitors of the hepatitis C virus [15], indoleamine 2,3-dioxygenase-1 (IDO1) inhibitors from structurebased virtual screening to in Vivo pharmacodynamic activity [16], anti-hypertensive agent [17], Zika Virus Inhibitors [18], in vitro alpha-glucosidase inhibitory [19], NOD2 antagonists [20], antiglycation and antioxidant [21] and antileukemic agents [22]. Surineni G. et al. considered that the benzimidazole core were used with excellent efficiency for the treatment of tuberculosis [23]. Recently, benzimidazole scaffolds were reported as anti-cancer agents in a diverse review [24,25]. As a consequence, diverse drugs originated from benzimidazole system have been introduced into the market cover albendazole (antimicrobial), omeprazole (Anti-ulcer), Bendamustine (Anti-tumor), Enviradine (Anti-viral), Candesartan (Antihypertensive) and Benoxaprofen Analog (Antiinflammatory) [26]. On the other hand, benzimidazoles nucleus gained diverse applications, particularly, they extensively Egyptian Journal of Chemistry http://ejchem.journals.ekb.eg/ 314 Fahad Alminderej and Lotfi Aroua _____________________________________________________________________________________________________________ ________________________________________________ Egypt. J. Chem. 64, No. 7 (2021) 3352 used as ligands in the development of the metal complex. Among, a diverse of benzimidazole complexes were reviewed and manifested several significant biological activities covering antibacterial [27], antifungal [28], antioxidant activity against DPPH and antidiabetic activity against -amylase [29], antiameobic [30], Potent inhibition of protein tyrosine phosphatases [31] and antimalarial [32]. Furthermore, the Schiff base elaborated from 2(1H-benzimizadol-2-yl)aniline and 2hydroxysalisaldehyde was recognized as an essential precursor leading the synthesis of diversely metal complexes owning therapeutic potential including antibacterial [33], analgesic and anti-inflammatory [34], and anticancer [35]. The architecture complex involving 2-((methyl-benzimidazol-2-phenyl) imino methyl) phenol have been also a multitude of applications as chemosensors [36-38]. Moreover, 2-(1H-benzimizadol-2-yl) aniline was reviewed as important of targeted owning a broad range of applications in different fields. In particular, a complex established with 2-hydroxynaphtaldehyde is well described in medicinal chemistry as anticancer [39]. In recent years, cancerous disease has been regarded as one of the public health problems in many countries, and research in this area has thus greatly increased. A variety of drugs was introduced in the market covering Paclitaxel known as Taxol used to treat a number of cancer including ovarian cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer and pancreatic cancer [40]. Docetaxel (known as Taxotere) is a chemotherapy medication used against a number of cancers. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cell lung cancer [41]. Bevacizumab, (Avastin) is a drug employed against colon cancer, lung cancer, glioblastoma, and renalcell carcinoma [42]. In continuation to develop and discover a novel molecular architecture possessing biological activities [43-48], we report the synthesis and anti-cancer evaluation of new mixed metal copper complexes derived from 2-aminomethylbenzothiazole, 2aminomethylbenzothiazole and Schiff base of 2-(1Hbenzimizadol-2-yl)aniline as ligand.