Synthesis, X-ray molecular structure, biological evaluation and molecular docking studies of some N⁴-benzyl substituted 5-nitroisatin-3-thiosemicarbazones

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• 作者：Humayun Pervez^a ; ^{pdhpervez@hotmail.com} ; Nazia Khan^a ; Sumera Zaib^b ; Muhammad Yaqub^a ; Muhammad Moazzam Naseer^c ; Muhammad Nawaz Tahir^d ; Jamshed Iqbal^b ; ^{drjamshed@ciit.net.pk}
• 关键词：Cytotoxicity ; 5-Nitroisatin ; Phytotoxicity ; Thiosemicarbazones ; Urease inhibition ; Urease inhibitors
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：25
• 期：3
• 页码：1022-1029
• 全文大小：775 K
• 卷排序：25

文摘

A series of fifteen N4-benzyl substituted 5-nitroisatin-3-thiosemicarbazones 5a–o was synthesized and evaluated for urease inhibitory, phytotoxic and cytotoxic influences. All the compounds proved to be highly potent inhibitors of the enzyme, showing inhibitory activity (IC50 = 0.87 ± 0.25–8.09 ± 0.23 μM) much better than the reference inhibitor, thiourea (IC50 = 22.3 ± 1.12 μM) and may thus act as persuasive leads for further studies. In phytotoxicity assay, twelve out of fifteen thiosemicarbazones tested i.e. 5a–e, 5g, 5i and 5k–o appeared to be active, exhibiting weak or non-significant (5–35%) growth inhibition at the highest tested concentrations (1000 or 500 μg/mL). In contrast, only one compound i.e. 5i was active in the brine shrimp (Artemia salina) lethality bioassay, demonstrating cytotoxic activity with LD50 value 2.55 × 10−5 M. Molecular docking studies of compounds 5a–o were also performed to identify their probable binding modes in the active site of the enzyme.