Design, synthesis and biological evaluation of chalconyl blended triazole allied organosilatranes as giardicidal and trichomonacidal agents

作者：Singh Gurjaspreet^*; Arora Aanchal; Mangat Satinderpal Singh; Rani Sunita; Kaur Hargobinder; Goya Kapil; Sehgal Rakesh; Maurya Indresh Kumar; Tewari Rupinder; Choquesillo Lazarte Duane; Sahoo Subash; Kaur Navneet

来源：European Journal of Medicinal Chemistry, 2016, 108: 287-300.

DOI：10.1016/j.ejmech.2015.11.029

• Chalcone
• 1,2,3-Triazole
• Silatrane
• Giardicidal activity
• Trichomonacidal activity
• Metronidazole
• 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazolium bromide (MTT)

A series of chalconyl blended triazole allied silatranes (7a-g/8a-g/9a-g) were synthesized in good yields using a simple, economical and biocompatible synthetic route. The blend of three different pharmacologically active moieties into a single scaffold resulted into synergistic effect in their bioactivity. Various substitutions were tried to study the structure activity relationship (SAR) of the synthesized compounds on the basis of biological results. All the newly synthesized compounds were well characterized by IR, H-1 and C-13 NMR, low resolution mass spectroscopy and elemental analysis. The structures of 7a and 7c were authenticated by single crystal X-ray crystallography. These compounds were screened by using Molinspiration software for their physicochemical properties and all the compounds showed good oral bioavailability. The antiparasitic activity of the newly synthesized compounds was evaluated against unicellular parasites (Giardia lamblia and Trichomonas vaginalis) in comparison to standard drug (metronidazole) by 3-(4,5-dimethylthiazol-yl)-diphenyl tetrazolium bromide (MTT) assay. All the compounds displayed significant activity against G. lamblia and T. vaginalis with IC50 values ranging from 19.58-131.2 mu M to 18.24-101.26 mu M respectively. The entire library of compounds was found to be more active than metronidazole except 9a, 9f and 9g. Notably, 9e and 7e were found to be most significant against G. lamblia and T vaginalis respectively.

• 出版日期2016-1-27
• 单位河北医科大学