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In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis -benzimidazole derivatives (1–25) by using 3,3′-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (h CA-IX) was evaluated in-vitro , where several synthesized derivatives showed potent inhibition of h CA-IX (IC 50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 μM) and compounds 3–5 , 7–8 , 13–16 , 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC 50 = 18.24 ± 1.43 μM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents. [ABSTRACT FROM AUTHOR]

In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis -benzimidazole derivatives (1–25) by using 3,3′-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (h CA-IX) was evaluated in-vitro , where several synthesized derivatives showed potent inhibition of h CA-IX (IC 50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 μM) and compounds 3–5 , 7–8 , 13–16 , 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC 50 = 18.24 ± 1.43 μM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents. [ABSTRACT FROM AUTHOR]

We report synthesis, characterization and anti-cancer activities of four new magnesium, calcium and strontium complexes containing 1, 10 – phenanthroline, p-amino benzoic acid and cinnamic acid. [Display omitted] Reactions of 1,10-phenanthroline (phen), p-amino benzoic acid (paba) and cinnamic acid (cina) with MCO 3 (M = Mg, Ca, Sr) yielded two mononuclear magnesium complexes [{Mg(phen)(H 2 O) 4 }(phen)(paba) 2 ] (1) and [{Mg(phen)(H 2 O) 4 }(phen)(cina) 2 ] (2) and two one dimensional chains of both calcium and strontium [Ca(phen)(cina)] n (3), and [Sr(phen)(cina)] n (4) respectively. The structures were characterized by a variety of analytical techniques including IR, UV–Vis, 1H NMR, elemental analysis, and single crystal X–ray diffraction analysis. In these complexes, phen binds via an N,Ń –chelate pocket, while the monoanionic paba— / cina— ligands either remains uncoordinated (in case of 1 and 2) or coordinated in a tridentate fashion (in case of 3 and 4). Complexes 1 , 3 and 4 crystallize in the same orthorhombic space group Pbcn while complex 2 crystallizes in triclinic space group P 1. In complex 1 and 2 , Mg2+ cation adopts a distorted six-coordinate octahedral geometry comprising an [N 2 O4] donor set while in complexes 3 and 4 , Ca2+ and Sr2+ cations adopt a distorted eight-coordinate geometry comprising [N2O6] donor sets. Complexes 1, 2 and 4 were found to be potent anticancer against oral cancer cell line i.e. CAL-27 with IC 50 1.85 ± 0.11 , 2.98 ± 1.2 and 5.05 ± 0.35 respectively while complex 3 was inactive. [ABSTRACT FROM AUTHOR]