TY  - JOUR
AU  - Sovari, Sara Nasiri
AU  - Kolly, Isabelle
AU  - Schindler, Kevin
AU  - Đurić, Ana
AU  - Srdić-Rajić, Tatjana
AU  - Crochet, Aurelien
AU  - Pavić, Aleksandar
AU  - Zobi, Fabio
PY  - 2023
UR  - https://pubs.rsc.org/en/content/articlelanding/2023/dt/d2dt04041g
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1981
AB  - We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to understand if the presence and position of a reactive halomethyl substituent on the diimine ligand system of fac-[Re(CO)3]+ species may be a key molecular feature for the design of active and non-toxic anticancer agents. Only compounds potentially able to undergo ligand-based alkylating reactions show significant antiproliferative activity against colorectal and pancreatic cell lines. Of the new species presented in this study, one compound (5-(chloromethyl)-2,2′-bipyridine derivative) shows significant inhibition of pancreatic tumour growth in vivo in zebrafish-Panc-1 xenografts. The complex is noticeably effective at 8 μM concentration, lower than its in vitro IC50 values, being also capable of inhibiting in vivo cancer cells dissemination.
T2  - Dalton Transactions
T1  - Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes
EP  - 6944
IS  - 20
SP  - 6934
VL  - 52
DO  - 10.1039/D2DT04041G
ER  - 

@article{
author = "Sovari, Sara Nasiri and Kolly, Isabelle and Schindler, Kevin and Đurić, Ana and Srdić-Rajić, Tatjana and Crochet, Aurelien and Pavić, Aleksandar and Zobi, Fabio",
year = "2023",
abstract = "We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to understand if the presence and position of a reactive halomethyl substituent on the diimine ligand system of fac-[Re(CO)3]+ species may be a key molecular feature for the design of active and non-toxic anticancer agents. Only compounds potentially able to undergo ligand-based alkylating reactions show significant antiproliferative activity against colorectal and pancreatic cell lines. Of the new species presented in this study, one compound (5-(chloromethyl)-2,2′-bipyridine derivative) shows significant inhibition of pancreatic tumour growth in vivo in zebrafish-Panc-1 xenografts. The complex is noticeably effective at 8 μM concentration, lower than its in vitro IC50 values, being also capable of inhibiting in vivo cancer cells dissemination.",
journal = "Dalton Transactions",
title = "Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes",
pages = "6944-6934",
number = "20",
volume = "52",
doi = "10.1039/D2DT04041G"
}

Sovari, S. N., Kolly, I., Schindler, K., Đurić, A., Srdić-Rajić, T., Crochet, A., Pavić, A.,& Zobi, F.. (2023). Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. in Dalton Transactions, 52(20), 6934-6944.
https://doi.org/10.1039/D2DT04041G

Sovari SN, Kolly I, Schindler K, Đurić A, Srdić-Rajić T, Crochet A, Pavić A, Zobi F. Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. in Dalton Transactions. 2023;52(20):6934-6944.
doi:10.1039/D2DT04041G .

Sovari, Sara Nasiri, Kolly, Isabelle, Schindler, Kevin, Đurić, Ana, Srdić-Rajić, Tatjana, Crochet, Aurelien, Pavić, Aleksandar, Zobi, Fabio, "Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes" in Dalton Transactions, 52, no. 20 (2023):6934-6944,
https://doi.org/10.1039/D2DT04041G . .

TY  - JOUR
AU  - Sovari, Sara Nasiri
AU  - Kolly, Isabelle
AU  - Schindler, Kevin
AU  - Cortat, Youri
AU  - Liu, Shing-Chi
AU  - Crochet, Aurelien
AU  - Pavić, Aleksandar
AU  - Zobi, Fabio
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1459
AB  - The reaction of rhenium alpha-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)(2)(NO)(N-N)X](+) species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)(2)(NO)(N-N)X](+) is that of a hard Re acid, probably due to the stronger pi-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for pi-basic ligands, which are consequently difficult to replace by, e.g., sigma-donor or weak pi-acids like pyridine. Attempts of direct nitrosylation of alpha-diimine fac-[Re(CO)(3)](+) complexes bearing pi-basic OR-type ligands gave the [Re(CO)(2)(NO)(N-N)(BF4)][BF4] salt as the only product in good yield, featuring a stable Re-FBF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)(2)(NO)(N-N)X](+) complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.
PB  - MDPI, Basel
T2  - Molecules
T1  - Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release
IS  - 17
VL  - 26
DO  - 10.3390/molecules26175302
ER  - 

@article{
author = "Sovari, Sara Nasiri and Kolly, Isabelle and Schindler, Kevin and Cortat, Youri and Liu, Shing-Chi and Crochet, Aurelien and Pavić, Aleksandar and Zobi, Fabio",
year = "2021",
abstract = "The reaction of rhenium alpha-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)(2)(NO)(N-N)X](+) species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)(2)(NO)(N-N)X](+) is that of a hard Re acid, probably due to the stronger pi-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for pi-basic ligands, which are consequently difficult to replace by, e.g., sigma-donor or weak pi-acids like pyridine. Attempts of direct nitrosylation of alpha-diimine fac-[Re(CO)(3)](+) complexes bearing pi-basic OR-type ligands gave the [Re(CO)(2)(NO)(N-N)(BF4)][BF4] salt as the only product in good yield, featuring a stable Re-FBF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)(2)(NO)(N-N)X](+) complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release",
number = "17",
volume = "26",
doi = "10.3390/molecules26175302"
}

Sovari, S. N., Kolly, I., Schindler, K., Cortat, Y., Liu, S., Crochet, A., Pavić, A.,& Zobi, F.. (2021). Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release. in Molecules
MDPI, Basel., 26(17).
https://doi.org/10.3390/molecules26175302

Sovari SN, Kolly I, Schindler K, Cortat Y, Liu S, Crochet A, Pavić A, Zobi F. Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release. in Molecules. 2021;26(17).
doi:10.3390/molecules26175302 .

Sovari, Sara Nasiri, Kolly, Isabelle, Schindler, Kevin, Cortat, Youri, Liu, Shing-Chi, Crochet, Aurelien, Pavić, Aleksandar, Zobi, Fabio, "Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release" in Molecules, 26, no. 17 (2021),
https://doi.org/10.3390/molecules26175302 . .

TY  - JOUR
AU  - Sovari, Sara Nasiri
AU  - Radaković, Nataša
AU  - Roch, Paul
AU  - Crochet, Aurelien
AU  - Pavić, Aleksandar
AU  - Zobi, Fabio
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1477
AB  - Antimicrobial resistance (AMR) is a major emerging threat to public health, causing serious issues in the successful prevention and treatment of persistent diseases. While the problem escalates, lack of financial incentive has lead major pharmaceutical companies to interrupt their antibiotic drug discovery programs. The World Health Organisation (WHO) has called for novel solutions outside the traditional development pathway, with emphasis on new classes of active compounds with non-classical mechanisms of action. Metal complexes are an untapped source of antibiotic potential owing to unique modes of action and a wider range of three-dimensional geometries as compared to purely organic compounds. In this study, we present the antimicrobial and antifungal efficacy of a family of rhenium tricarbonyl diimine complexes with varying ligands, charge and lipophilicity. Our study allowed the identification of potent and non-toxic complexes active in vivo against S. aureus infections at MIC doses as low as 300 ng/mL, as well as against C. albicans-MRSA mixed co-infection. The compounds are capable of suppressing the C. albicans morphogenetic yeast-to-hyphal transition, eradicating fungal-S. aureus co-infection, while showing no sign of cardio-, hepato-, hematotoxiciy or teratogenicity.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection
VL  - 226
DO  - 10.1016/j.ejmech.2021.113858
ER  - 

@article{
author = "Sovari, Sara Nasiri and Radaković, Nataša and Roch, Paul and Crochet, Aurelien and Pavić, Aleksandar and Zobi, Fabio",
year = "2021",
abstract = "Antimicrobial resistance (AMR) is a major emerging threat to public health, causing serious issues in the successful prevention and treatment of persistent diseases. While the problem escalates, lack of financial incentive has lead major pharmaceutical companies to interrupt their antibiotic drug discovery programs. The World Health Organisation (WHO) has called for novel solutions outside the traditional development pathway, with emphasis on new classes of active compounds with non-classical mechanisms of action. Metal complexes are an untapped source of antibiotic potential owing to unique modes of action and a wider range of three-dimensional geometries as compared to purely organic compounds. In this study, we present the antimicrobial and antifungal efficacy of a family of rhenium tricarbonyl diimine complexes with varying ligands, charge and lipophilicity. Our study allowed the identification of potent and non-toxic complexes active in vivo against S. aureus infections at MIC doses as low as 300 ng/mL, as well as against C. albicans-MRSA mixed co-infection. The compounds are capable of suppressing the C. albicans morphogenetic yeast-to-hyphal transition, eradicating fungal-S. aureus co-infection, while showing no sign of cardio-, hepato-, hematotoxiciy or teratogenicity.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection",
volume = "226",
doi = "10.1016/j.ejmech.2021.113858"
}

Sovari, S. N., Radaković, N., Roch, P., Crochet, A., Pavić, A.,& Zobi, F.. (2021). Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 226.
https://doi.org/10.1016/j.ejmech.2021.113858

Sovari SN, Radaković N, Roch P, Crochet A, Pavić A, Zobi F. Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection. in European Journal of Medicinal Chemistry. 2021;226.
doi:10.1016/j.ejmech.2021.113858 .

Sovari, Sara Nasiri, Radaković, Nataša, Roch, Paul, Crochet, Aurelien, Pavić, Aleksandar, Zobi, Fabio, "Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection" in European Journal of Medicinal Chemistry, 226 (2021),
https://doi.org/10.1016/j.ejmech.2021.113858 . .

TY  - JOUR
AU  - Sovari, Sara Nasiri
AU  - Vojnović, Sandra
AU  - Škaro Bogojević, Sanja
AU  - Crochet, Aurelien
AU  - Pavić, Aleksandar
AU  - Nikodinović-Runić, Jasmina
AU  - Zobi, Fabio
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1365
AB  - We have prepared a series of ten 3-arylcoumarin molecules, their respective fac-[Re(CO)(3)(bpy)L](+) and fac-[Re(CO)(3)(L(sic)L)Br] complexes and tested all compounds for their antimicrobial efficacy. Whereas the 3-arylcoumarin ligands are virtually inactive against the human-associated pathogens with minimum inhibitory concentrations (MICs)  gt  150 mu M, when coordinated to the fac-[Re(CO)(3)](+) core, most of the resulting complexes showed remarkable antibacterial potency. Several rhenium complexes exhibit activity in nanomolar concentrations against Gram-positive pathogens such as Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA) and Enterococcus faecium. The molecules do not affect bacterial cell membrane potential, but some of the most potent complexes strongly interact with DNA, indicating it as a possible target for their mode of action. In vivo studies in the zebrafish model showed that the complexes with anti-staphylococcal/MRSA activity were non-toxic to the organism even at much higher doses of the corresponding MICs. In the zebrafish-MRSA infection model, the complexes increased the survival rate of infected fish up to 100% and markedly reduced bacterial burden. Moreover, all rescued fish developed normally following the treatments with the metallic compounds.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)
VL  - 205
DO  - 10.1016/j.ejmech.2020.112533
ER  - 

@article{
author = "Sovari, Sara Nasiri and Vojnović, Sandra and Škaro Bogojević, Sanja and Crochet, Aurelien and Pavić, Aleksandar and Nikodinović-Runić, Jasmina and Zobi, Fabio",
year = "2020",
abstract = "We have prepared a series of ten 3-arylcoumarin molecules, their respective fac-[Re(CO)(3)(bpy)L](+) and fac-[Re(CO)(3)(L(sic)L)Br] complexes and tested all compounds for their antimicrobial efficacy. Whereas the 3-arylcoumarin ligands are virtually inactive against the human-associated pathogens with minimum inhibitory concentrations (MICs)  gt  150 mu M, when coordinated to the fac-[Re(CO)(3)](+) core, most of the resulting complexes showed remarkable antibacterial potency. Several rhenium complexes exhibit activity in nanomolar concentrations against Gram-positive pathogens such as Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA) and Enterococcus faecium. The molecules do not affect bacterial cell membrane potential, but some of the most potent complexes strongly interact with DNA, indicating it as a possible target for their mode of action. In vivo studies in the zebrafish model showed that the complexes with anti-staphylococcal/MRSA activity were non-toxic to the organism even at much higher doses of the corresponding MICs. In the zebrafish-MRSA infection model, the complexes increased the survival rate of infected fish up to 100% and markedly reduced bacterial burden. Moreover, all rescued fish developed normally following the treatments with the metallic compounds.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)",
volume = "205",
doi = "10.1016/j.ejmech.2020.112533"
}

Sovari, S. N., Vojnović, S., Škaro Bogojević, S., Crochet, A., Pavić, A., Nikodinović-Runić, J.,& Zobi, F.. (2020). Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 205.
https://doi.org/10.1016/j.ejmech.2020.112533

Sovari SN, Vojnović S, Škaro Bogojević S, Crochet A, Pavić A, Nikodinović-Runić J, Zobi F. Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). in European Journal of Medicinal Chemistry. 2020;205.
doi:10.1016/j.ejmech.2020.112533 .

Sovari, Sara Nasiri, Vojnović, Sandra, Škaro Bogojević, Sanja, Crochet, Aurelien, Pavić, Aleksandar, Nikodinović-Runić, Jasmina, Zobi, Fabio, "Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)" in European Journal of Medicinal Chemistry, 205 (2020),
https://doi.org/10.1016/j.ejmech.2020.112533 . .

TY  - JOUR
AU  - Rossier, Jeremie
AU  - Sovari, Sara Nasiri
AU  - Pavić, Aleksandar
AU  - Vojnović, Sandra
AU  - Stringer, Tameryn
AU  - Battig, Sarah
AU  - Smith, Gregory S.
AU  - Nikodinović-Runić, Jasmina
AU  - Zobi, Fabio
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1276
AB  - We have explored the possibility of using organometallic derivatives of cobalamin as a scaffold for the delivery of the same antimalarial drug to both erythro- and hepatocytes. This hybrid molecule approach, intended as a possible tool for the development of multi-stage antimalarial agents, pivots on the preparation of azide-functionalized drugs which, after coupling to the vitamin, are released with a 4-(4-ethynylphenyl)-triazole functionality. Three chloroquine and one imidazolopiperazine derivative (based on the KAF156 structure) were selected as model drugs. One hybrid chloroquine conjugate was extensively studied via fluorescent labelling for in vitro and in vivo bio-distribution studies and gave proof-of-concept for the design. It showed no toxicity in vivo (zebrafish model) as well as no hepatotoxicity, no cardiotoxicity or developmental toxicity of the embryos. All 4-(4-ethynylphenyl)-triazole derivatives of chloroquine were equally active against chloroquine-resistant (CQR) and chloroquine-sensitive (CQS) Plasmodium falciparum strains.
PB  - MDPI, Basel
T2  - Molecules
T1  - Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins
IS  - 12
VL  - 24
DO  - 10.3390/molecules24122310
ER  - 

@article{
author = "Rossier, Jeremie and Sovari, Sara Nasiri and Pavić, Aleksandar and Vojnović, Sandra and Stringer, Tameryn and Battig, Sarah and Smith, Gregory S. and Nikodinović-Runić, Jasmina and Zobi, Fabio",
year = "2019",
abstract = "We have explored the possibility of using organometallic derivatives of cobalamin as a scaffold for the delivery of the same antimalarial drug to both erythro- and hepatocytes. This hybrid molecule approach, intended as a possible tool for the development of multi-stage antimalarial agents, pivots on the preparation of azide-functionalized drugs which, after coupling to the vitamin, are released with a 4-(4-ethynylphenyl)-triazole functionality. Three chloroquine and one imidazolopiperazine derivative (based on the KAF156 structure) were selected as model drugs. One hybrid chloroquine conjugate was extensively studied via fluorescent labelling for in vitro and in vivo bio-distribution studies and gave proof-of-concept for the design. It showed no toxicity in vivo (zebrafish model) as well as no hepatotoxicity, no cardiotoxicity or developmental toxicity of the embryos. All 4-(4-ethynylphenyl)-triazole derivatives of chloroquine were equally active against chloroquine-resistant (CQR) and chloroquine-sensitive (CQS) Plasmodium falciparum strains.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins",
number = "12",
volume = "24",
doi = "10.3390/molecules24122310"
}

Rossier, J., Sovari, S. N., Pavić, A., Vojnović, S., Stringer, T., Battig, S., Smith, G. S., Nikodinović-Runić, J.,& Zobi, F.. (2019). Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins. in Molecules
MDPI, Basel., 24(12).
https://doi.org/10.3390/molecules24122310

Rossier J, Sovari SN, Pavić A, Vojnović S, Stringer T, Battig S, Smith GS, Nikodinović-Runić J, Zobi F. Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins. in Molecules. 2019;24(12).
doi:10.3390/molecules24122310 .

Rossier, Jeremie, Sovari, Sara Nasiri, Pavić, Aleksandar, Vojnović, Sandra, Stringer, Tameryn, Battig, Sarah, Smith, Gregory S., Nikodinović-Runić, Jasmina, Zobi, Fabio, "Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins" in Molecules, 24, no. 12 (2019),
https://doi.org/10.3390/molecules24122310 . .