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Preparation of dried nanoemulsion formulation by electrospinning
No full textDry eye disease is a multifactorial condition characterized by a loss of homeostasis of the tear film. Among the various treatment approaches, the application of ophthalmic oil-in-water nanoemulsions with incorporated anti-inflammatory drugs represents one of the most advanced approaches. However, the liquid nature of nanoemulsions limits their retention time at the ocular surface. Transforming the nanoemulsions into a dry form that would disperse rapidly in the tear fluid would improve the retention of the drug at the ocular surface. The aim of this study was to investigate electrospinning as a method for the preparation of a solid eye preparation based on nanoemulsion loaded with the anti-inflammatory drug loteprednol etabonate. Four nanoemulsions differing in oil-to-surfactant ratios were incorporated in hydrophilic nanofibers based on polyethylene oxide, poloxamer 188, and Soluplus®. The dried nanoemulsions in the form of nanofibers dispersed readily on contact with aqueous medium, resulting in a dispersion of nanometre-sized droplets with average size comparable to the average droplet size of the initial nanoemulsions. A rheological study revealed the predominant elastic behavior of the dispersed nanofibers, which indicates the formation of a weak gel after the dispersion of the dried nanoemulsion in tear fluid at the ocular surface. The biocompatibility of the dried nanoemulsions in the form of nanofibers after a single and multiple-dose application was confirmed using the 3D HCE-T model of the stratified epithelium of the human cornea, suggesting that this innovative solid eye preparation could represent a new approach to the treatment of dry eye disease
Identification and quantification of bioactive compounds in commercially available Punica granatum L. extracts
No full textU okviru ovog diplomskog rada istraživane su bioaktivne sastavnice šest komercijalnih ekstrakata
vrste Punica granatum L. Tankoslojnom kromatografijom (TLC) nije dokazana značajna prisutnost
flavonoida i fenolnih kiselina. UV-Vis spektrofotometrijskom metodom određen je sadržaj
flavonoida i fenolnih kiselina koji je iznosio redom 0,0009 – 0,0119 % i 0,1275 – 1,1041 %.
Tekućinskom kromatografijom visoke djelotvornosti (HPLC) u uzorcima koncentracije 5 mg/mL
nije detektiran vitamin C. Antiradikalna aktivnost uzoraka dokazana je sposobnošću hvatanja DPPH
i NO radikala.Bioactive compounds of six commercially available Punica granatum L. extracts were examined in
this thesis. Thin Layer Chromatography (TLC) did not show significant amount of flavonoids and
phenolic acids. Quantification of flavonoids and phenolic acids was done using UV-Vis
spectrophotometry and the amounts ranged from 0,0009 – 0,0119 % and 0,1275 – 1,1041 %,
respectively. High-performance liquid chromatography (HPLC) was used to quantify vitamin C in
5 mg/mL extract solutions and did not detect any. Antiradical activity was proven with DPPH and
NO scavenging methods
Physical-chemical characterization of food supplements containing Aloe vera
No full textUpalne bolesti crijeva kronične su, inflamatorne i idiopatske bolesti karakterizirane ponavljajućim epizodama upale gastrointestinalnog trakta zbog abnormalnog imunološkog odgovora na crijevnu mikrofloru. U posljednje vrijeme primjena dodataka prehrani sve je učestalija posebice kod pacijenata koji boluju od kroničnih bolesti poput upalnih bolesti crijeva. Američka farmakopeja sadrži priznate standarde identiteta, snage, kvalitete, čistoće, pakiranja i označavanja ljekovitih tvari, oblika doziranja i drugih terapeutskih proizvoda, uključujući dodatke prehrani.
Cilj ovog diplomskog rada bilo je provjeriti zadovoljavaju li dodaci prehrani koji sadrže Aloe veru zahtjeve Američke farmakopeje s obzirom na fizikalno-kemijsku karakterizaciju gotovih dozirnih oblika. Provedeno ispitivanje pokazuje kako ispitani uzorci tableta, tvrdih i mekih kapsula zadovoljavaju uvijete Američke farmakopeje.Inflammatory bowel diseases are chronic, inflammatory and idiopathic diseases characterized by recurrent episodes of inflammation of the gastrointestinal tract due to an abnormal immune response to the intestinal microflora. In recent times, the use of nutritional supplements has become increasingly popular, especially in patients suffering from chronic diseases such as inflammatory bowel diseases. The US Pharmacopoeia contains recognized standards for the identity, strength, quality, purity, packaging, and labeling of medicinal substances, dosage forms, and other therapeutic products, including dietary supplements.
The aim of this thesis was to check whether food supplements containing Aloe vera meet the requirements of the American Pharmacopoeia regarding the physical-chemical characterization of the finished dosage forms. The conducted testing shows that the tested samples of tablets, hard and soft capsules meet the requirements of the American Pharmacopoeia
Biological activity of broadleaf plantain (Plantago major L.) glycerol extracts rich in polyphenols and verbascoside for application in cosmetics
No full textBiljne vrste bogate biološki aktivnim sastavnicama predmetom su brojnih istraživanja zbog svojih pozitivnih učinaka na kožu i potencijalne primjene u kozmetičkim formulacijama. U prethodnim istraživanjima razvijene su (optimizirane) dvije metode ekstrakcije nadzemnih dijelova širokolisnog trputca (P. major L., Plantaginaceae), pomoću vodene otopine glicerola i mliječne kiseline. Prvom metodom je postignuta maksimalna količina ukupnih polifenola, a drugom maksimalna količina verbaskozida u priređenim ekstraktima OPT-TP odnosno OPT-VER. U ovom radu provedeno je istraživanje antioksidativne aktivnosti priređenih ekstrakata te inhibitorne aktivnosti prema enzimima koji utječu na izgled i zdravlje kože. Antioksidativna aktivnost određena je pomoću antiradikalne 2,2-difenil-1-pikrilhidrazil (DPPH) metode, a biološki učinci ispitani su enzimskim testovima inhibicije elastaze, kolagenaze, hijaluronidaze i tirozinaze. Ispitani ekstrakti pokazali su iznimno dobar antioksidativni potencijal, nadmašivši pritom aktivnost butilhidroksianisola, koji je korišten kao pozitivna kontrola. Najbolja biološka aktivnost ekstrakata ostvarena je u testu inhibicije kolagenaze. Nadalje, utvrđena je značajna inhibicija hijaluronidaze, umjerena sposobnost inhibicije elastaze te blaga inhibicija tirozinaze. Ekstrakt OPT-TP postigao je veću aktivnost u svim biološkim ispitivanjima, osim u testu inhibicije kolagenaze, gdje je aktivniji bio OPT-VER. Također, u odnosu na OPT-TP, OPT-VER pokazao je nešto veću sposobnost hvatanja slobodnih radikala u DPPH antioksidativnoj analizi.Plant species rich in biologically active components are the subject of numerous studies due to their positive effects on the skin and potential application in cosmetic formulations. In previous research, two methods using aqueous solution of glycerol and lactic acid were developed (optimized) for extraction of broadleaf plantain (P. major L., Plantaginaceae) aerial parts. The first method achieved maximum quantity of total polyphenols, and the other maximum quantity of verbascoside in the corresponding extracts (OPT-TP and OPT-VER). In this work, the antioxidant activity of the prepared extracts and the inhibitory activity against enzymes that affect the appearance and health of the skin were investigated. Antioxidant activity was determined using the antiradical 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and biological effects were examined by enzymatic assays of elastase, collagenase, hyaluronidase and tyrosinase inhibition. Tested extracts showed extremely notable antioxidant potential, surpassing the activity of butylhydroxyanisole, which was used as a positive control. The best biological activity of the extracts was achieved in the collagenase inhibition test. Furthermore, a significant inhibition of hyaluronidase, a moderate ability to inhibit elastase and a slight inhibition of tyrosinase was established. Extract OPT-TP achieved greater activity in all biological tests, except in the collagenase inhibition test, where OPT-VER was more active. Also, compared to OPT-TP, OPT-VER showed a slightly higher ability to capture free radicals in the DPPH antioxidant assay
The impact of the chemokine axis CCR6/CCL20 on the progression of autoimmune diseases and cancer
No full textRegulacija imunološkog odgovora ključna je za održavanje ravnoteže između učinkovitog
obrambenog mehanizma i sprječavanja autoimunosti ili prekomjerne upale. Poremećena regulacija
može dovesti do razvoja kroničnih upalnih stanja, autoimunosnih bolesti i karcinoma. Kronične
bolesti predstavljaju jedan od najvećih javnozdravstvenih izazova današnjice zbog rastuće
prevalencije i složenosti etiologije. Svojom kompleksnošću, ove su bolesti i dalje nedovoljno
istraženo područje čime se nameće potreba za daljnjim istraživanjima i pronalaskom novih
terapijskih meta.
Kemokini imaju ključnu ulogu u imunološkom odgovoru. Oni reguliraju migraciju imunoloških
stanica prema mjestima upale i sudjeluju u modulaciji imunološke ravnoteže. Među brojnim
kemokinima, CCR6/CCL20 kemokinska os ističe se svojom ulogom u koordinaciji normalnih i
patoloških procesa. Dominantna uloga CCR6/CCL20 kemokinske osi u imunološkoj regulaciji
ovisi o preciznoj ekspresiji CCR6 receptora na Th17 i Treg staničama ključnima za održavanje
ravnoteže između proupalnoga i protuupalnoga stanja. U uvjetima homeostaze, ova os pomaže u
održavanju imunološke tolerancije putem Treg stanica. Treg stanice koje nose CCR6 receptor,
mogu migrirati prema upalnim područjima bogatim CCL20 kemokinom, gdje potom proliferiraju
i ispoljavaju svoje imunosupresivne funkcije. U uvjetima narušene ravnoteže, promjena ekspresije
CCR6/CCL20 osi može dovesti do disbalansa između Th17 i Treg stanica, što može rezultirati
prekomjerenom upalom, autoimunošću ili poticanju tumorskoga mikrookruženja. Cilj ovog
diplomskog rada bio je dati jasan pregled mehanizama djelovanja CCR6/CCL20 osi i naglasiti
njezinu ključnu ulogu u progresiji autoimunosnih bolesti i karcinoma
The use of transgenic plants in vaccine production
No full textProizvodnja cjepiva moguća je pomoću transgeničnih biljaka, odnosno unosom gena od interesa u genom
biljke i posljedičnom ekspresijom ciljanog rekombinantnog proteina. Metode proizvodnje uključuju stabilnu
i prolaznu ekspresiju unutar biljnog tkiva. Postoje različite biljke koje su kandidati za domaćina, a najčešće
korišten je duhan jer zadovoljava najviše uvjeta za proizvodnju. Iako je ovaj način proizvodnje slabije istražen
i još uvijek ima nedostatke, postoje metode za poboljšanje proizvodnje koje se sve više razvijaju i omogućuju
veći prinos i ekspresiju proteina veće imunogenosti. Cilj proizvodnje u biljkama je lakša proizvodnja,
uključujući minimalnu obradu i izostanak potrebe za skupim bioreaktorima te hladnim uvjetima skladištenja
i transporta. Također je važna mogućnost cijepljenja u zemljama u razvoju i brza proizvodnja koja omogućuje
adekvatnu brzinu reakcije u slučaju pandemije ili bioterorizma. Trenutno je registrirano samo cjepivo za
veterinarsku uporabu, ali je više cjepiva za različite patogene u procesu kliničkih ispitivanja.The production of vaccines is possible using transgenic plants, i.e. by introducing the gene of interest into the
plant's genome and the consequent expression of the target recombinant protein. Production methods include
stable and transient expression within plant tissue. There are different plants that are candidates for the host,
and the most used is tobacco because it meets the most criteria for production. Although this method of
production is less well researched and still has drawbacks, there are methods to improve production that are
increasingly being developed and allow higher yield and expression of proteins with higher immunogenicity.
The goal of production in plants is easier production, including minimal processing and the absence of the
need for expensive bioreactors and cold storage and transport conditions. Also important is the possibility of
vaccination in developing countries and fast production, which enables an adequate reaction speed in the
event of a pandemic or bioterrorism. Currently, the only registered vaccine is for veterinary use, but more
vaccines for different pathogens are in the process of clinical trials
The impact of postoperative antihormonal therapy with anastrozole and tamoxifen on N-glycosylation patterns of IGG in women with breast cancer
No full textRak dojke trenutno je najčešće dijagnosticirani tip raka u žena. Trenutne metode nedovoljno dobro prate i
predviđaju reakcije pacijenata na liječenje antihormonskim lijekovima, izlažući pacijente potencijalno
nepoželjnim nuspojavama tih lijekova. N-glikani plazmatskih proteina i imunoglobulina G (IgG) pokazani su kao
biomarkeri mnogobrojnih bolesti, posebno onih s izraženim upalnim ili metaboličkim komponentama poput
dijabetesa, hipertenzije, kardiovaskularnih bolesti i raka. Ovo istraživanje istraživalo je strukturne promjene Nglikana
IgG-a prateći 40 pacijenata s rakom dojke Luminal A i Luminal B podtipova tijekom najviše 9 mjeseci.
Protokol je uključivao novorazvijeni automatizirani protokol koji je uključivao izolaciju IgG, denaturaciju
proteina, fluorescentno obilježavanje glikana, pročišćavanje i konačnu analizu pomoću kapilarne gel elektroforeze
s laserski induciranom fluorescencijom. Rezultati su sugerirali značajnu ulogu modificiranih glikana u progresiji
raka dojke, otkrivajući karakteristične trendove u načinu na koji anastrozol i tamoksifen izazivaju različite reakcije.
Rezultati upućuju na povezanost anastrozola sa smanjenom sijalilacijom i povećanom sržnom fukozilacijom, dok
je tamoksifen korelirao s povećanom sijalilacijom i smanjenom sržnom fukozilacijom. Ova promatranja sugeriraju
potencijalne imunomodulatorne učinke: anastrozol potencijalno slabije smanjuje upalu sistemskim smanjenjem
razina estrogena, dok tamoksifen svojim specifičnijim djelovanjem direktno manje utječe na razine estrogena u
tijelu i proizvodi manji proupalni učinak. Ovo istraživanje snažno naglašava važnost uzimanja u obzir specifičnih
karakteristika glikana kako bi se razumjeli dinamični mehanizmi koji potiču progresiju raka dojke i učinci ciljanih
terapija.Breast cancer is currently the most commonly diagnosed type of cancer in women. Current methods inadequately
track and predict patient reactions to antihormonal treatments, exposing patients to potentially undesirable side
effects of these drugs. N-glycans of plasma proteins and immunoglobulin G (IgG) have been shown as biomarkers
for numerous diseases, especially those with pronounced inflammatory or metabolic components such as diabetes,
hypertension, cardiovascular diseases, and cancer. This study investigated structural changes in IgG N-glycans in
40 patients with Luminal A and Luminal B subtypes of breast cancer over a maximum of 9 months. The protocol
included a newly developed automated procedure involving IgG isolation, protein denaturation, glycan fluorescent
labeling, purification, and final analysis using capillary gel electrophoresis with laser-induced fluorescence. The
results suggested a significant role of modified glycans in breast cancer progression, revealing characteristic trends
in how anastrozole and Tamoxifen induce different reactions. The results indicate the association of anastrozole
with reduced sialylation and increased core fucosylation, while Tamoxifen correlated with increased sialylation
and decreased core fucosylation. These observations suggest potential immunomodulatory effects: Anastrozole
potentially reduces inflammation less by systemically lowering estrogen levels, while Tamoxifen, with its more
specific action, directly affects estrogen levels in the body less and produces a lesser pro-inflammatory effect. This
study strongly emphasizes the importance of considering specific glycan characteristics to understand the dynamic
mechanisms driving breast cancer progression and the effects of targeted therapies
Botanička obilježja, kemijski sastav i upotreba vrste Desmodium gangeticum (L.) DC.
No full textDesmodium gangeticum (L.) DC. is a well-known medicinal
plant that is widely used in Indian indigenous medicine systems
such as Ayurveda to treat a variety of diseases. The plant belongs to the family
Fabaceae and is native to tropical regions of Asia, Australia, and Africa. This
species’ phytochemical analysis revealed the presence of numerous phytoconstituents, including alkaloids, flavonoids, pterocarpans, sterols, and others. Pterocarpan gangetin is studied the most because of its anti-implantation activity.
Various in vitro and in vivo pharmacological tests demonstrated Desmodium
gangeticum’s ability to exhibit antimicrobial, antioxidant, antiamnestic, cardioprotective, anti-cancer, anti-ulcer, anti-diabetic, and antiinflammatory properties. This plant is an important candidate species for future drug discovery due to its wide range of biological activities. Plant extracts are not toxic even in high
doses, making it interesting from a pharmacological perspective
Development of a bioanalytical method for the determination of cyclin D dependent kinase 4 and 6 inhibitors and other drugs in therapeutic combinations for HR+/HER2− breast cancer treatment
No full textRak dojke, kao jedan od najčešće dijagnosticiranih tumora u svijetu, velik je javnozdravstveni problem. Liječenje se nastoji unaprijediti razvojem novih lijekova, ali i personaliziranim pristupom postojećoj terapiji s obzirom na specifične karakteristike pacijentica kroz postupak terapijskog praćenja lijekova (engl. therapeutic drug monitoring, TDM). Temeljni preduvjeti TDM-u su provedena istraživanja farmakokinetičkih parametara u ciljanoj populaciji te povezanosti doze lijeka, njegove koncentracije u plazmi ili drugom tkivu i učinka ili toksičnosti. Za sve navedeno potrebna je prikladna, selektivna i osjetljiva bioanalitička metoda. U ovom doktorskom radu proveden je razvoj uvjeta pripreme uzorka ljudske plazme, kromatografskog razdvajanja i detekcije šest lijekova – kandidata za TDM: inhibitora o ciklinu D ovisnih kinaza 4 i 6 (CDK4/6) palbocikliba, ribocikliba, abemacikliba, inhibitora aromataze anastrozola i letrozola te selektivnog degradatora estrogenskih receptora fulvestranta. Ispitana su i optimizirana četiri različita pristupa pripremi složenog biološkog uzorka za analizu: taloženje proteina, disperzivna tekućinska mikroekstrakcija, ekstrakcija na čvrstoj fazi i pročišćavanje uklanjanjem fosfolipida. Razvijene su i validirane četiri nove kromatografske metode za razdvajanje lijekova od interesa primjenom fenilne i bifenilne stacionarne faze na različitim kromatografskim sustavima. Evaluacija pročišćavanja uzorka plazme od apsorbirajućih interferencija provedena je robusnim detektorom niza dioda i detektorom fluorescencije, dok su klinički relevantni linearni rasponi i praćenje zaostalih plazmatskih fosfolipida postignuti osjetljivim spektrometrima masa s analizatorom kvadrupola i vremena leta ili trostrukog kvadrupola. Provedena je validacija optimiziranih metoda u skladu s međunarodno prihvaćenim smjernicama, kao i unakrsna validacija naprednijih metoda pročišćavanja na istom kromatografskom sustavu i setu realnih uzoraka pacijentica. Ekološka i ekonomska svojstva razvijenih metoda vrednovana su primjenom Red-Green-Blue-12 (RGB-12), Analytical Greenness Metric (AGREE, AGREEprep) i Blue Applicability Grade Index (BAGI) alata. Naposlijetku, sve validirane metode su uspješno primijenjene za određivanje koncentracija te procjenu farmakokinetičkih parametara lijekova od interesa u stvarnim uzorcima pacijentica. Time je kao rezultat ovog doktorskog istraživanja stvorena potrebna bioanalitička podloga, kao i demonstrirana njena praktična valjanost za implementaciju u kliničkoj praksi u svrhu provođenja daljnjih ispitivanja TDM-a šest lijekova od interesa radi poboljšanja skrbi i terapijskih ishoda za pacijentice s rakom dojke.Breast cancer, as one of the most diagnosed tumours in the world, presents a significant public health issue. Treatment options are being expanded with the development of new drugs and the personalisation of existing therapies based on patient-specific characteristics through therapeutic drug monitoring (TDM). The main prerequisites for TDM include gaining insight into pharmacokinetic parameters in the target population and establishing correlations between drug dose, its plasma or tissue concentration, and therapeutic or toxic effects. A selective and sensitive bioanalytical method is key to achieving these objectives. In this doctoral thesis the development of human plasma sample preparation conditions, chromatographic separation, and detection were performed for six drugs – candidates for TDM: cyclin D dependent kinase 4 and 6 (CDK4/6) inhibitors palbociclib, ribociclib, and abemaciclib, aromatase inhibitors anastrozole and letrozole, and the selective estrogen receptor degrader fulvestrant. Four different approaches for the preanalytical preparation of complex biological samples were tested and optimised: protein precipitation, dispersive liquid-liquid microextraction, solid-phase extraction and phospholipid removal. Additionally, four chromatographic methods for analyte separation on phenyl and biphenyl stationary phases were developed and validated using different chromatographic systems. Plasma sample cleanup from absorbing interferences was evaluated using robust diode-array and fluorescence detectors, while clinically relevant linear ranges and monitoring of leftover plasma phospholipids were achieved using sensitive mass spectrometers with quadrupole-time-of-flight or triple-quadrupole mass analysers. Method validation was conducted in accordance with internationally accepted guidelines, and cross-validation of advanced sample preparation methods was performed on the same chromatographic system with a set of real patient samples. The ecological and economic properties of the methods were assessed using Red-Green-Blue-12 (RGB-12), Analytical Greenness Metric (AGREE, AGREEprep) and Blue Applicability Grade Index (BAGI) tools. Finally, all validated methods were successfully applied to quantify the drugs of interest and estimate their pharmacokinetic parameters in real patient samples. As the main result of this doctoral research, the necessary bioanalytical foundation has been established and its practical feasibility for implementation in the clinical practice has been demonstrated, with the aim of facilitating further research on TDM for the drugs of interest, ultimately improving patient care and treatment outcomes for breast cancer patients
Synthesis and characterization of 1,2,3 - triazole Beta-carbolinr and primaquine derivatives
No full textβ-Karbolini su velika skupina prirodnih i sintetskih spojeva koju karakterizira heterociklički prsten
koji se sastoji od indola i piridina. Biološko djelovanje β-karbolinia je raznoliko; npr. pokazali su
antimalarijsko, antibakterijsko i antiproliferativno djelovanje in vivo i in vitro. Pretpostavljen
mehanizam antimalarijskog djelovanja harmina kao nabolje istraženog β-karbolina je inhibicija
PfHsp90 proteina. Primakin je 8-aminokinolinski antimalarik koji je u primjeni od 1952. godine.
U ovom radu prikazana je sinteza dva nova derivata β-karbolina i primakina (6 i 7) koji su povezani
1,2,3-triazolskim prstenom s ciljem dobivanja derivata poboljšane učinkovitosti. Kao početni spoj
u sintezi korišten je metilni ester triptofana koji je Pictet-Spenglerovom reakcijom u mikrovalnom
reaktoru preveden u tetrahidro-β-karbolin (1). Oksidacijom spoja 1 uz Pd/C i Li2CO3 dobiven je
spoj 2 (6-metoksiharman) koji se kiselom hidrolizom prevodi u odgovarajući alkohol 3 (6-
hidroksiharman). Dobiveni alkohol se uz propargil bromid prevodi u spoj 4. Konačni produkti (6 i
7) sintetizirani su iz propargilnog derivata β-karbolina 4 i azida primakina 5 u reakciji Huisgenove
1,3-dipolarne cikloadicije.
Strukture sintetiziranih spojeva 6 i 7 potvrđene su standardnim analitičkim i spektroskopskim
metodama (1H i 13C NMR, IR, MS) i određeno im je talište.
Pomoću programskih alata SwissADME, Lipinskijevih i Veberovih pravila utvrđeno je da spoj 6
zadovoljava gotovo sva Lipinskijeva i Veberova pravila pa ima potencijala za razvoj kao novi
antimalarijski lijek.
Sintetiziranim spojevima 6 i 7 će u daljnjim istraživanjima biti ispitano biološko djelovanje.β-Carbolines are a large group of natural and synthetic compounds characterized by a heterocyclic
ring consisting of indole and pyridine. The biological effects of β-carbolines are diverse; for
example, they showed antimalarial, antibacterial, and antiproliferative activity in vivo and in vitro.
Assumed mechanism of antimalarial action of harmine, the best-studied β-carboline, is inhibition of
the PfHsp90 protein. Primaquine is an 8-aminoquinoline antimalarial that has been used since 1952.
This research describes synthesis of two new derivates of β-carboline and primaquine linked with
1,2,3-triazole bridge with the aim of obtaining derivatives with improved activity. The initial
compound for the synthesis was tryptophan methyl ester, which was converted to tetrahydro-βcarboline 1 by the Pictet-Spengler reaction in a microwave reactor. Oxidation of compound 1 with
Pd/C and Li2CO3 gave compound 2 (6-methoxyharman), which was converted to the corresponding
alcohol 3 (6-hydroxyharman) by acid hydrolysis. The β-carboline alcohol 3 was converted to
compound 4 with propargyl bromide. The target products (6 and 7) were synthesized from the
propargylated β-carboline derivative 4 and primaquine azide 5 in the Huisgen 1,3-dipolar
cycloaddition.
The structures of synthesized compounds 6 and 7 were confirmed by standard analytical and
spectroscopic methods (1H and 13C NMR, IR, MS), and their melting points were determined.
Using the SwissADME software and Lipinski and Weber rules, compound 6 was found to satisfy
almost all Lipinski and Weber rules and thus has the potential to be a new antimalarial drug.
The biological activity of synthesized compounds 6 and 7 will be tested in further studies