The synthesis of aminobenzimidazoles has been demonstrated under mild reaction conditions using cobalt catalyst in one pot reaction. This methodology involved domino intra and intermolecular C-N cross-coupling reaction. In addition, functional group tolerance has been also explored.Benzimidazoles [1][2][3][4][5][6][7][8][9][10] and 2-aminobenzimidazoles [11][12][13][14][15][16][17][18][19][20][21] are very powerful compounds because of their applications in therapeutic [22][23] and biological sciences ( Figure 1). [24][25] These compounds were used as neuropeptide YY1 receptor antagonist, [26] N-methyl-D-aspartate (NMDA) antagonist, [27] factor Xa(FXa) inhibitor, [28] poly(ADP-ribose)polymerase (PARP) inhibitor [29] and non-peptide thrombin inhibitor. [30] In addition, these compounds show anti-inflammatory, antimicrobial and antibacterial activities. [31] Apart from that, these compounds can also be used for the synthesis of dyes and high-temperature resistance polymers. [32] Therefore, the construction of benzimidazole derivatives were developed by many researchers via both traditional methods [33][34][35] and C-N cross-coupling reactions using various transition metals such as Cu, [36][37][38][39][40] Pd, [41][42][43] Co, [44] Zn, [45][46][47] and Ru. [48] In this connection, we would like to demonstrate the methodology for the synthesis of benzimidazoles from thiourea in one pot reaction via desulphurization/substitution/domino C-N cross-coupling reaction using cobalt source as catalyst under mild reaction conditions.

A rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for simultaneous quantification of silodosin and silodosin β-D-glucuronide human plasma using stable labelled isotopes as internal standards. Solid phase extraction technique (SPE) was used for the extraction and the method validated over a range of 0.20 ng/mL to 100.56 ng/mL for silidisin and 0.20 ng/mL to 101.63 ng/mL for silodosin β-D-glucuronide. The chromatographic separation was achieved on Cosmicsil Adze C18 (4.6 × 100 mm, 3 µm) column using a mobile phase consisting of acetonitrile, methanol and 10 mM ammonium acetate buffer 50:20:30 (v/v/v) at a flow rate of 1.000 mL/min with run time of 4 min. The API-4500 LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. The developed assay method was successfully applied to a pharmacokinetic study in humans.

Background: Mixed ligand copper complexes with 1,10-phenanthroline show good chemical nuclease activity and anticancer activity. Recently, tetrazole derivatives are also promising candidates for anticancer activity. Hence, it is significant to study the DNA binding and anticancer activity of two active N-donor ligands and their copper complexes. Objectives: The main objective of this study was to investigate the regioisomeric mixed ligand copper complexes response with calf thymus DNA binding and anti-toxic activity against MCF-7 cell line. Methods: The DNA binding interactions of complexes 1-4 with calf thymus DNA (CT-DNA) were monitored by UV/VIS spectroscopy. The absorption spectra of the Cu complexes are compared with and without CT-DNA at 400-450 nm. The cell proliferation was measured by using the standard 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay with four different concentrations of the compounds (5, 10, 50, and 100 mm) and cisplatin (as a positive control) was tested in triplicate for 48 h. The results obtained by the XTTassay are expressed as the average standard deviation of two experiments. The IC 50 values of the complexes exhibited differential and dose-dependent inhibitory activities on the growth of MCF-7 cancer cells. Results: Based on the elemental analysis, molar conductance, magnetic moments, mass, electronic, ESR and IR spectral data, the copper is coordinated by N-atoms of 1,10-phenanthroline and pyridyl tetrazole with octahedral structure. DFT calculations of HOMO and LUMO studies showed that electron density is localized on pyridyl tetrazole ring and phenanthroline ring. The calculated DNA binding constant (K b) values of 1-4 complexes are in the range 4.2-7.6 x10 4 M-1 (Table 4) with similar binding affinity to reported copper tetrazole derivative complexes. The 1-4 complexes with CT DNA interaction are through planar phenanthroline and pyridyl tetrazole ring likely via π-stacking interactions. The IC 50 values of complexes show excellent activity with 24(± 0.5); 18(± 0.5); 20(±0.5); (±0.5) and 38 (±0.8) for 1, 2, 3, 4 and cis platin complexes, respectively. After 72 h of the treatment of 1 on MCF-7 cell, IC 50 values hinder the cell growth upto 24(± 0.5) µg/ml at 5 µM concentration range (Fig. 5). It is apparent from IC 50 values that the order inhibition is 1 > 3 >2 > 4. Conclusion: Experimental results are highly encouraging to explore the mixed ligand regio isomeric copper complexes which have shown the parallel result with Cisplatin. By proper structural modification of pyridyl tetrazole ligand, substituent better anticancer agents can be prepared.

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