title: Synthesis, X-ray molecular structure, biological evaluation and molecular docking studies of some N4-benzyl substituted 5-nitroisatin-3-thiosemicarbazones.
abstract: 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±0.23μM) much better than the reference inhibitor, thiourea (IC50=22.3±1.12μM) 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 500μg/mL). In contrast, only one compound i.e. 5i was active in the brine shrimp (Artemia salina) lethality bioassay, demonstrating cytotoxic activity with LD50value 2.55×10-5M. Molecular docking studies of compounds 5a-o were also performed to identify their probable binding modes in the active site of the enzyme.
authors.affiliation: Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan. Electronic address: pdhpervez@hotmail.com.
authors.forename: Humayun
authors.initials: H
authors.lastname: Pervez
authors.affiliation: Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan.
authors.forename: Nazia
authors.initials: N
authors.lastname: Khan
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Sumera
authors.initials: S
authors.lastname: Zaib
authors.affiliation: Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yaqub
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Muhammad Moazzam
authors.initials: MM
authors.lastname: Naseer
authors.affiliation: Department of Physics, University of Sargodha, Sargodha 45320, Pakistan.
authors.forename: Muhammad Nawaz
authors.initials: MN
authors.lastname: Tahir
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D001156:Artemia / Q000166:cytology / Q000187:drug effects*; D032449:Canavalia / Q000201:enzymology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007510:Isatin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013882:Thiosemicarbazones; D007510:Isatin; D014510:Urease
keywords: 5-Nitroisatin; Cytotoxicity; Phytotoxicity; Thiosemicarbazones; Urease inhibition; Urease inhibitors