Toksičnost odabranih herbicida analizirana in silico metodama i biološkim testovima

doctoral thesis

• Title (english): Toxicitiy of selected herbicides analysed by in silico methods and bioassays
• Author: Vesna Pehar; VIAF: 42160242862452432079
• Mentor: Zrinka Kovarik (mentor)
• Mentor: Višnja Stepanić (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Branimir Bertoša (član povjerenstva)
• Committee member: Suzana Žunec (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-07-20, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Skup od 346 komercijalna herbicida prikupljen je iz dostupnih internetskih baza podataka, dok su 163 herbicida, koja nisu u primjeni, preuzeti iz literaturnih izvora te su oba skupa klasificirana prema mehanizmu djelovanja na korov (HRAC klasifikacija). In silico su predviđena fizikalno-kemijska svojstva i potencijal herbicida za toksično djelovanje na ljudsko zdravlje. Njihovom opsežnom analizom kao potencijalno najtoksičniji identificirani su spojevi iz klase K1, K3/N, F1 i E. Za in vitro analizu potencijalnih inhibitora acetilkolinesteraze i butirilkolinesteraze odabrano je 11 herbicida. Organofosfat anilofos (K3) i oksiacetanilid flufenacet (K3) bili su najpotentniji inhibitori obje kolinesteraze. Glifosat (G), oksadiazon (E), tembotrion (F2) i terbutilazin (C1) bili su vrlo slabi inhibitori kolinesteraza. Općenito, aktivni herbicidi imali su nešto veći potencijal za inhibiciju butirilkolinesteraze nego acetilkolinesteraze. Anilofos, benzulid (Z), butamifos (K1), piperofos (K3) i oksadiazon djelovali su citotoksično na ljudske živčane i jetrene stanice. Rezultati provedenih in silico i in vitro istraživanja daju uvid u potencijalnu toksičnost herbicida i moguću primjenu u dizajnu novih herbicida sigurnih za ljudsko zdravlje i okoliš.

Abstract (english)

Sets of 346 commercial and 163 outdated herbicides were collected from available internet databases and literature and classified according to their mode of action on weeds (HRAC classification). Potential toxic effects on human health and relevant physicochemical properties were predicted. By their extensive analysis the compounds from K1, K3/N, F1, and E classes were identified as the most risky. Eleven herbicides were selected for further in vitro study as potential acetylcholinesterase and butyrylcholinesterase inhibitors. The organophosphate anilophos (K3) and the oxyacetanilide flufenacet (K3) were found to be the most potent inhibitors of both cholinesterases. Glyphosate (G), oxadiazon (E), tembotrione (F2), and terbuthylazine (C1) were poor cholinesterase inhibitors. In general, the active herbicides showed slightly higher potential to inhibit butyrylcholinesterase. Anilophos, bensulide (Z), butamifos (K1), piperofos (K3), and oxadiazon showed cytotoxicity on human nerve and liver cells. The results of the study provide information on the potential toxicity of herbicides, and can be used in design of new herbicides with no toxicity to humans and the environment.

• Keywords: acetilkolinesteraza; anilofos; citotoksičnost; flufenacet; glifosat; inhibitori; organofosfati
• Keywords (english): acetylcholinesterase; anilophos; cytotoxicity; flufenacet; glyphosate; inhibitors; organophosphates
• Language: croatian
• URN:NBN: urn:nbn:hr:217:877075
• Promotion: 2023
• Project: Number: IP-2018-01-7683; Title: Analiza interakcija butirilkolinesteraze s novim inhibitorima i reaktivatorima; Acronym: AnalyseBChE; Leader: Zrinka Kovarik; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 99, XV str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-08-31 11:46:11