Ivković, Aleksandar

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  • Ivković, Aleksandar (3)
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Author's Bibliography

Chalcones are potential inhibitors of HIV-1 protease

Turković, Nemanja; Tasić, Milica; Kotur-Stevuljević, Jelena; Vujić, Zorica; Ivković, Branka; Ivković, Aleksandar

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Turković, Nemanja
AU  - Tasić, Milica
AU  - Kotur-Stevuljević, Jelena
AU  - Vujić, Zorica
AU  - Ivković, Branka
AU  - Ivković, Aleksandar
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4491
AB  - The discovery of HIV and the study of molecular mechanisms crucial for the virus
replication cycle have led to the identification of important protein structures - potential
targets of drug action in AIDS therapy. One of the most significant discoveries is HIV-1
protease (PR), an enzyme that plays a key role in the HIV replication cycle (1). This study
aimed to test and demonstrate the interactions of newly synthesized chalcones (1,3-diaryl-2-
propen-1-one) as well as three commercial drugs (lopinavir, ritonavir and darunavir) in the
active site of HIV-1 protease using in sillico methods. and that the results obtained correlate
with the results of in vitro tests on the enzyme itself. The twenty structurally similar
chalcone derivatives were synthesized and their physico-chemical characterization was
performed. Docking calculations were performed using the Autodock Wine program in the
3D structure of the enzime catalytic site (pdb code: 6B36). The inhibition of enzyme activity
was monitored by fluorimetric method (2). The obtained results revealed that all compounds
showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity
with an IC 50 values of 0.001 μM which is comparable with commercial product Darunavir.
The results obtained indicate that the synthesized compounds can be classified as potential
anti-HIV-1 protease inhibitors. Further research is focused on testing the ADMET properties
of the synthesized compounds as well as the synthesis of their analogues for which in silico
tests have shown satisfactory results.
AB  - Otkrić e HIV-a i istraživanje molekularnih mehanizama ključnih za ciklus replikacije
virusa dovelo je do identifikacije važnih proteinskih struktura - potencijalnih ciljnih mesta
dejstva lekova u terapiji AIDS-a. Jedno od najznačajnijih otkrića je HIV-1 proteaza (PR),
enzim koji ima ključnu ulogu u ciklusu replikacije HIV-a (1). Ova studija imala je za cilj da
primenom in sillico metoda ispita i prikaže interakcije novosintetisanih halkona (1,3-diaril-2-
propen-1-ona) kao i tri komercijalna leka (lopinavira, ritonavira i darunavira) u aktivnom
mestu HIV-1 proteaze i da dobijene rezultate koreliše sa rezultatima in vitro testova na
samom enzimu. Sintetisano je dvadeset strukturno sličnih derivata halkona i izvršena
njihova fizičko-hemijska karakterizacija. Docking studije izvedene su u programu Autodock
Vine u 3D strukturi enzimskog katalitičkog mesta (pdb kod: 6B36). Inhibicija enzimske
aktivnosti određena je primenom fluorimetrijske metode (2). Dobijeni rezultati ukazuju da
svih 20 jedinjenja ispoljava anti-HIV-1 proteaznu aktivnost. Jedinjenje HNT1 je pokazalo
najveć u inhibitornu aktivnost sa vrednostima IC50 od 0,001 μM što je uporedivo sa
komercijalnim proizvodom darunavirom. Dobijeni rezultati ukazuju da se sitetisana
jedinjenja mogu klasifikovati kao potencijalni anti-HIV-1 proteazni inhibitori. Dalje
istraživanje je usmereno na ispitivanju ADMET osobina sintetisanih jedinjenja kao i sintezi
njihovih analoga za koje su in silico ispitivanja pokazala zadovoljavajuće rezultate.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Chalcones are potential inhibitors of HIV-1 protease
T1  - Halkoni potencijalni inhibitori HIV‐1 proteaze
VL  - 72
IS  - 4 suplement
SP  - S186
EP  - S187
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4491
ER  - 
@conference{
author = "Turković, Nemanja and Tasić, Milica and Kotur-Stevuljević, Jelena and Vujić, Zorica and Ivković, Branka and Ivković, Aleksandar",
year = "2022",
abstract = "The discovery of HIV and the study of molecular mechanisms crucial for the virus
replication cycle have led to the identification of important protein structures - potential
targets of drug action in AIDS therapy. One of the most significant discoveries is HIV-1
protease (PR), an enzyme that plays a key role in the HIV replication cycle (1). This study
aimed to test and demonstrate the interactions of newly synthesized chalcones (1,3-diaryl-2-
propen-1-one) as well as three commercial drugs (lopinavir, ritonavir and darunavir) in the
active site of HIV-1 protease using in sillico methods. and that the results obtained correlate
with the results of in vitro tests on the enzyme itself. The twenty structurally similar
chalcone derivatives were synthesized and their physico-chemical characterization was
performed. Docking calculations were performed using the Autodock Wine program in the
3D structure of the enzime catalytic site (pdb code: 6B36). The inhibition of enzyme activity
was monitored by fluorimetric method (2). The obtained results revealed that all compounds
showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity
with an IC 50 values of 0.001 μM which is comparable with commercial product Darunavir.
The results obtained indicate that the synthesized compounds can be classified as potential
anti-HIV-1 protease inhibitors. Further research is focused on testing the ADMET properties
of the synthesized compounds as well as the synthesis of their analogues for which in silico
tests have shown satisfactory results., Otkrić e HIV-a i istraživanje molekularnih mehanizama ključnih za ciklus replikacije
virusa dovelo je do identifikacije važnih proteinskih struktura - potencijalnih ciljnih mesta
dejstva lekova u terapiji AIDS-a. Jedno od najznačajnijih otkrića je HIV-1 proteaza (PR),
enzim koji ima ključnu ulogu u ciklusu replikacije HIV-a (1). Ova studija imala je za cilj da
primenom in sillico metoda ispita i prikaže interakcije novosintetisanih halkona (1,3-diaril-2-
propen-1-ona) kao i tri komercijalna leka (lopinavira, ritonavira i darunavira) u aktivnom
mestu HIV-1 proteaze i da dobijene rezultate koreliše sa rezultatima in vitro testova na
samom enzimu. Sintetisano je dvadeset strukturno sličnih derivata halkona i izvršena
njihova fizičko-hemijska karakterizacija. Docking studije izvedene su u programu Autodock
Vine u 3D strukturi enzimskog katalitičkog mesta (pdb kod: 6B36). Inhibicija enzimske
aktivnosti određena je primenom fluorimetrijske metode (2). Dobijeni rezultati ukazuju da
svih 20 jedinjenja ispoljava anti-HIV-1 proteaznu aktivnost. Jedinjenje HNT1 je pokazalo
najveć u inhibitornu aktivnost sa vrednostima IC50 od 0,001 μM što je uporedivo sa
komercijalnim proizvodom darunavirom. Dobijeni rezultati ukazuju da se sitetisana
jedinjenja mogu klasifikovati kao potencijalni anti-HIV-1 proteazni inhibitori. Dalje
istraživanje je usmereno na ispitivanju ADMET osobina sintetisanih jedinjenja kao i sintezi
njihovih analoga za koje su in silico ispitivanja pokazala zadovoljavajuće rezultate.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Chalcones are potential inhibitors of HIV-1 protease, Halkoni potencijalni inhibitori HIV‐1 proteaze",
volume = "72",
number = "4 suplement",
pages = "S186-S187",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4491"
}
Turković, N., Tasić, M., Kotur-Stevuljević, J., Vujić, Z., Ivković, B.,& Ivković, A.. (2022). Chalcones are potential inhibitors of HIV-1 protease. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S186-S187.
https://hdl.handle.net/21.15107/rcub_farfar_4491
Turković N, Tasić M, Kotur-Stevuljević J, Vujić Z, Ivković B, Ivković A. Chalcones are potential inhibitors of HIV-1 protease. in Arhiv za farmaciju. 2022;72(4 suplement):S186-S187.
https://hdl.handle.net/21.15107/rcub_farfar_4491 .
Turković, Nemanja, Tasić, Milica, Kotur-Stevuljević, Jelena, Vujić, Zorica, Ivković, Branka, Ivković, Aleksandar, "Chalcones are potential inhibitors of HIV-1 protease" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S186-S187,
https://hdl.handle.net/21.15107/rcub_farfar_4491 .

Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill

Adamov, Ivana; Medarević, Đorđe; Ivković, Branka; Ivković, Aleksandar; Ibrić, Svetlana

(Pharmaceutical Association of Serbia, 2022)

TY  - JOUR
AU  - Adamov, Ivana
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Ivković, Aleksandar
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4411
AB  - Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm
shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to
the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets
using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and
warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated
with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and
poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of
8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were
successfully printed, as well as combined two-layered 3D tablets, with each of the active
substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but
incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of
HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs
from the combined two-layered 3D tablets was observed. The absence of drug-polymer
interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP
technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further
optimization of formulation factors is necessary to achieve complete drug release.
AB  - Uvođenje tehnologije 3D štampe u oblasti farmacije uslovilo je razvoj fundamentalnih promena, pri čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama lekova prilagođenih prema specifičnim potrebama pacijenata. Cilj istraživanja bio je da se formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP). Hidrohlortiazid (HHT, 5%, m/m) i varfarin-natrijum (WS, 5%, m/m) odabrani su kao model lekovite supstance. Proces štampanja sproveden je u prisustvu 0,1% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. Jednoslojne 3D tablete prečnika 8,00 mm i debljine 1,50 mm, koje sadrže HHT, odnosno WS, kao i kombinovane dvoslojne 3D tablete, sa svakom od aktivnih supstanci u posebnom sloju, uspešno su odštampane. Prilikom ispitivanja brzine rastvaranja lekovite supstance iz jednoslojnih tableta, došlo je do trenutnog (81,47±1,47%, nakon 45 min), ali nepotpunog oslobađanja WS, i produženog i potpunog oslobađanja HHT (98,17±3,11%, nakon 8 h), dok je iz kombinovanih tableta zapaženo znatno sporije i nepotpuno oslobađanje obe lekovite supstance. Potvrđeno je odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika pruža mogućnost jednostavne i brze izrade kombinovanih tableta, pri čemu je dalja optimizacija formulacionih faktora neophodna u cilju postizanja potpunog oslobađanja lekovite supstance.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill
T1  - 3D tehnika digitalne obrade svetlosti (DLP) primenjena u izradi dvoslojnih tableta: koncept kombinovane polipilule
VL  - 72
IS  - 6
SP  - 674
EP  - 688
DO  - 10.5937/arhfarm72-40365
ER  - 
@article{
author = "Adamov, Ivana and Medarević, Đorđe and Ivković, Branka and Ivković, Aleksandar and Ibrić, Svetlana",
year = "2022",
abstract = "Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm
shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to
the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets
using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and
warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated
with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and
poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of
8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were
successfully printed, as well as combined two-layered 3D tablets, with each of the active
substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but
incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of
HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs
from the combined two-layered 3D tablets was observed. The absence of drug-polymer
interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP
technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further
optimization of formulation factors is necessary to achieve complete drug release., Uvođenje tehnologije 3D štampe u oblasti farmacije uslovilo je razvoj fundamentalnih promena, pri čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama lekova prilagođenih prema specifičnim potrebama pacijenata. Cilj istraživanja bio je da se formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP). Hidrohlortiazid (HHT, 5%, m/m) i varfarin-natrijum (WS, 5%, m/m) odabrani su kao model lekovite supstance. Proces štampanja sproveden je u prisustvu 0,1% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. Jednoslojne 3D tablete prečnika 8,00 mm i debljine 1,50 mm, koje sadrže HHT, odnosno WS, kao i kombinovane dvoslojne 3D tablete, sa svakom od aktivnih supstanci u posebnom sloju, uspešno su odštampane. Prilikom ispitivanja brzine rastvaranja lekovite supstance iz jednoslojnih tableta, došlo je do trenutnog (81,47±1,47%, nakon 45 min), ali nepotpunog oslobađanja WS, i produženog i potpunog oslobađanja HHT (98,17±3,11%, nakon 8 h), dok je iz kombinovanih tableta zapaženo znatno sporije i nepotpuno oslobađanje obe lekovite supstance. Potvrđeno je odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika pruža mogućnost jednostavne i brze izrade kombinovanih tableta, pri čemu je dalja optimizacija formulacionih faktora neophodna u cilju postizanja potpunog oslobađanja lekovite supstance.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill, 3D tehnika digitalne obrade svetlosti (DLP) primenjena u izradi dvoslojnih tableta: koncept kombinovane polipilule",
volume = "72",
number = "6",
pages = "674-688",
doi = "10.5937/arhfarm72-40365"
}
Adamov, I., Medarević, Đ., Ivković, B., Ivković, A.,& Ibrić, S.. (2022). Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 674-688.
https://doi.org/10.5937/arhfarm72-40365
Adamov I, Medarević Đ, Ivković B, Ivković A, Ibrić S. Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill. in Arhiv za farmaciju. 2022;72(6):674-688.
doi:10.5937/arhfarm72-40365 .
Adamov, Ivana, Medarević, Đorđe, Ivković, Branka, Ivković, Aleksandar, Ibrić, Svetlana, "Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill" in Arhiv za farmaciju, 72, no. 6 (2022):674-688,
https://doi.org/10.5937/arhfarm72-40365 . .
2

Ring closing metathesis/fragmentation route to (Z)-configured medium ring cycloalkenes. Total synthesis of (+/-)-periplanone C

Matović, Radomir; Ivković, Aleksandar; Manojlović, Marija; Tokić-Vujošević, Zorana; Saičić, Radomir N.

(Amer Chemical Soc, Washington, 2006)

TY  - JOUR
AU  - Matović, Radomir
AU  - Ivković, Aleksandar
AU  - Manojlović, Marija
AU  - Tokić-Vujošević, Zorana
AU  - Saičić, Radomir N.
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/685
AB  - The combination of ring closing metathesis and beta-fragmentation offers an efficient entry into (Z)-configured medium ring cycloalkenes. The fragmentation step can be effected under anionic or radical conditions. The versatility of this method is demonstrated by the total synthesis of (+/-)-periplanone C - a macrocyclic pheromone of Periplaneta americana.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Organic Chemistry
T1  - Ring closing metathesis/fragmentation route to (Z)-configured medium ring cycloalkenes. Total synthesis of (+/-)-periplanone C
VL  - 71
IS  - 25
SP  - 9411
EP  - 9419
DO  - 10.1021/jo061790j
ER  - 
@article{
author = "Matović, Radomir and Ivković, Aleksandar and Manojlović, Marija and Tokić-Vujošević, Zorana and Saičić, Radomir N.",
year = "2006",
abstract = "The combination of ring closing metathesis and beta-fragmentation offers an efficient entry into (Z)-configured medium ring cycloalkenes. The fragmentation step can be effected under anionic or radical conditions. The versatility of this method is demonstrated by the total synthesis of (+/-)-periplanone C - a macrocyclic pheromone of Periplaneta americana.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Organic Chemistry",
title = "Ring closing metathesis/fragmentation route to (Z)-configured medium ring cycloalkenes. Total synthesis of (+/-)-periplanone C",
volume = "71",
number = "25",
pages = "9411-9419",
doi = "10.1021/jo061790j"
}
Matović, R., Ivković, A., Manojlović, M., Tokić-Vujošević, Z.,& Saičić, R. N.. (2006). Ring closing metathesis/fragmentation route to (Z)-configured medium ring cycloalkenes. Total synthesis of (+/-)-periplanone C. in Journal of Organic Chemistry
Amer Chemical Soc, Washington., 71(25), 9411-9419.
https://doi.org/10.1021/jo061790j
Matović R, Ivković A, Manojlović M, Tokić-Vujošević Z, Saičić RN. Ring closing metathesis/fragmentation route to (Z)-configured medium ring cycloalkenes. Total synthesis of (+/-)-periplanone C. in Journal of Organic Chemistry. 2006;71(25):9411-9419.
doi:10.1021/jo061790j .
Matović, Radomir, Ivković, Aleksandar, Manojlović, Marija, Tokić-Vujošević, Zorana, Saičić, Radomir N., "Ring closing metathesis/fragmentation route to (Z)-configured medium ring cycloalkenes. Total synthesis of (+/-)-periplanone C" in Journal of Organic Chemistry, 71, no. 25 (2006):9411-9419,
https://doi.org/10.1021/jo061790j . .
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