Synthesis, DNA binding and biological evaluation of benzimidazole Schiff base ligands and their metal(ii) complexes.

Two novel benzimidazole ligands (E)-2-((4-(1H-benzo[d]imidazole-2-yl)phenylimino)methyl)-6-bromo-4-chlorophenol (L1) and (E)-1-((4-(1H-benzo[d]imidazole-2-yl)phenylimino)methyl)naphthalene-2-ol (L2) with their corresponding Cu(ii), Ni(ii), Pd(ii) and Zn(ii) complexes were designed and synthesized. The compounds were characterized by elemental, IR, and NMR (1H & 13C) spectral analyses. Molecular masses were determined by ESI-mass spectrometry, and the structure of ligand L1 was confirmed by single crystal X-ray diffraction analysis. Molecular docking was carried out for the theoretical investigation of DNA binding interactions. The results obtained were verified experimentally by UV/Visible absorption spectroscopy in conjunction with DNA thermal denaturation studies. It was observed that ligands (L1 and L2) and complexes (1-8) were moderate to strong DNA binders, as evident from the binding constants (K b). The value was found to be highest for complex 2 (3.27 × 105 M-1) and lowest for 5 (6.40 × 103 M-1). A cell line study revealed that breast cancer cells were less viable to the synthesized compounds compared to that of standard drugs, cisplatin and doxorubicin, at the same concentration. The compounds were also screened for in vitro antibacterial activity for which complex 2 showed a promising broad-spectrum effect against all tested strains of bacteria, almost in the proximity of the reference drug kanamycin, while the rest of the compounds displayed activity against selected strains.

Synthesis, crystal structures, Hirshfeld surface analysis and spectroscopic studies of two Schiff bases of anisaldehyde and their urease and acetylcholinesterase inhibitory and antioxidant properties.

The growing demand of pharmaceutical industry for more effective drugs requires new molecules with promising medicinal activities. In the present work, a natural product anisaldehyde was treated with hydrazine and 3,5-dichloroaniline to synthesize their Schiff bases, ASB1 and ASB2, which were assessed for various bioactivities. ASB1 was synthesized by conventional reflux method while ASB2 was synthesized by reflux as well as by mechanochemical grinding method which gave higher yield. The bases were recrystalised, and their structures were elucidated based on XRD and spectroscopic studies. Hirshfeld surface analysis was also carried out. They showed considerable urease inhibitory activity, almost comparable with the standard thiourea. The activity of ASB1 was much higher than ASB2. Acetylcholinesterase inhibitory activity of ASB1 was also higher than that of ASB2. The antioxidant activities were determined using DPPH, ABTS radical scavenging and total antioxidant capacity (TAC) assays. The bases were very poor scavengers of DPPH radical. However, they showed considerable anti-radical activity against ABTS radical, ASB2 being more active than ASB1, while ASB1 showed higher TAC than ASB2. In conclusion, the bases appeared to have good drugability as inhibitors of urease and acetylcholinesterase enzymes. They can be easily synthesized for possible large-scale applications. The grinding method proved to be more efficient than the reflux method.

Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines.

Thymidine phosphorylase (TP) is an angiogenic enzyme. It plays an important role in angiogenesis, tumour growth, invasion and metastasis. In current research work, we study the effect of structural modification of dihydropyrimidine-2-ones (DHPM-2-ones) on TP inhibition. A series of eighteen new derivatives of 3,4-dihydropyrimidone-2-one were designed and synthesized through the structural modification at C-6 position. All these new derivatives were then assessed for in-vitro inhibition of thymidine phosphorylase (TP) from E. coli. Oxadiazole derivatives 4a-e exhibited excellent TP-inhibition at low micromolar concentration levels better than standard drug 7-deazaxanthine (7-DX). Among all these compounds, 4b was found to be the most potent with IC50 = 1.09 ±â€¯0.004 µM. Anti-angiogenesis potential of representative compounds were also studied in a chorioallantoic membrane (CAM) assay. Here again, compound 4b was found to be the potent anti-angiogenesis compound in a CAM assay. Docking studies were also performed with Molecular Operating Environment (MOE) to further analyse the mode of inhibition of these compounds. Binding mode analysis of the most active inhibitors showed that these are well accommodated into the binding site of enzyme though stable hydrogen bonding and hydrophobic interactions.