Sinteza i karakterizacija bis-urea primakina s aminoalkoholima

master's thesis

• Title (english): Synthesis and charaterization of primaquine bis-ureas with aminoalcohols
• Author: Hrvoje Boić
• Mentor: Kristina Pavić (mentor)
• Committee member: Kristina Pavić (predsjednik povjerenstva)
• Committee member: Mirela Matić (član povjerenstva)
• Committee member: Zrinka Rajić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2018-05-30, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Malarija je smrtonosna parazitska bolest tropskih i subtropskih krajeva koja se prenosi ubodom komarca roda Anopheles, a uzrokovana je vrstama roda Plasmodium. Primakin je antimalarik koji djeluje na tkivne shizonte te je jedini dostupni hipnozoitocid, a djeluje i na gametocite svih vrsta plazmodija koji uzrokuju malariju kod čovjeka. S druge strane, istraživanja pokazuju da poznati antimalarici, uključujući primakin, imaju i citostatsko djelovanje na maligne stanične linije. Stoga primakin predstavlja vrlo zanimljivu molekulu pogodnu za derivatizaciju u potrazi za novim citostaticima.
Ovaj rad je nastavak dugogodišnjih istraživanja derivata primakina u Zavodu za farmaceutsku kemiju Sveučilišta u Zagrebu Farmaceutsko-biokemijskog fakulteta. Rezultati prethodnih istraživanja temelj su dizajniranja novih bis-urea primakina kao potencijalnih citostatika i/ili antimalarika koje u svojoj strukturi sadrže alifatski ciklički ili aromatski aminoalkohol. Sintetizirane su dvije bis-uree 5a-b koje su karakterizirane uobičajenim analitičkim i spektroskopskim metodama (IR, MS, 1H i 13C NMR). Oba spoja zadovoljavaju gotovo sve kriterije dane Lipinskijevim i Gelovanijevim pravilima, odnosno kriterijima Bioavailability radara (SwissADME) za male molekule. Trenutno su u tijeku ispitivanja citostatskog, antimalarijskog i antituberkuloznog djelovanja sintetiziranih spojeva koja prelaze okvire ovog rada.

Abstract (english)

Malaria is a life-threatening parasitic disease of tropic and sub-tropic areas transmitted through the bite of infected Anopheles mosquito, caused by protozoa Plasmodium. Primaquine is an antimalarial drug effective on tissue schizonts and only hypnozoitocide available, also effective against gametocytes all plasmodiums that cause disease in humans. Furthermore, researches indicate that well-known antimalarials, including primaquine, have anticancer activity on malignant cell lines. Therefore, primaquine presents a fascinating molecule suitable for further derivatization in search for new anticancer drugs.
This paper is a continuum of longtime research on new primaquine derivatives as potential anticancer agents at University of Zagreb Department of Medicinal Chemistry. Results of past research represent a base for the design of novel primaquine bis-ureas as potential antimalarial or anticancer agents with aliphatic cyclic or aromatic aminoalcohol moieties in their structure. Newly synthesized primaquine bis-ureas 5a-b are characterized using classical analytical and spectroscopic methods (IR, MS, 1H and 13C NMR). Both novel compounds have a good drug-likeness score, with most of them meeting all of the Lipinski’s and/or Gelovani’s rules, as well as criteria given by the Bioavailability radar (SwissADME) for small molecules. Evaluation of their anticancer, antimalarial and antitubercular activity is in progress.

• Keywords: primakin; bis-urea; malarija; rak; aminoalkoholi
• Keywords (english): primaquine; bis-urea; malaria; cancer; aminoalcohols
• Language: croatian
• URN:NBN: urn:nbn:hr:163:900035
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-10-01 11:39:35