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Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or mefloquine (MQ) scaffolds and β-carboline alkaloid harmine against cancer cell lines and <italic>Plasmodium falciparum</italic>. The hybrids were prepared from the corresponding amines by 1,1′-carbonyldiimidazole (CDI)-mediated synthesis. <italic>In vitro</italic> evaluation of the biological activity of the title compounds revealed two hit compounds. Testing of the antiproliferative activity of the new UT harmiquins, and previously prepared triazole-(TT) and amide-type (AT) CQ-based harmiquins, against a panel of human cell lines, revealed TT harmiquine <bold>16</bold> as the most promising compound, as it showed pronounced and selective activity against the tumor cell line HepG2 (<italic>IC</italic>50 = 5.48 ± 3.35 μmol L−1). Screening of the antiplasmodial activities of UT harmiquins against erythrocytic stages of the <italic>Plasmodium</italic> life cycle identified CQ-based UT harmiquine <bold>12</bold> as a novel antiplasmodial hit because it displayed low <italic>IC</italic>50 values in the submicromolar range against CQ-sensitive and resistant strains (<italic>IC</italic>50 0.06 ± 0.01, and 0.19 ± 0.02 μmol L−1, respectively), and exhibited high selectivity against <italic>Plasmodium</italic>, compared to mammalian cells (SI = 92).
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Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or mefloquine (MQ) scaffolds and β-carboline alkaloid harmine against cancer cell lines and Plasmodium falciparum. The hybrids were prepared from the corresponding amines by 1,1′-carbonyldiimidazole (CDI)-mediated synthesis. In vitro evaluation of the biological activity of the title compounds revealed two hit compounds. Testing of the antiproliferative activity of the new UT harmiquins, and previously prepared triazole-(TT) and amide-type (AT) CQ-based harmiquins, against a panel of human cell lines, revealed TT harmiquine 16 as the most promising compound, as it showed pronounced and selective activity against the tumor cell line HepG2 (IC50 = 5.48 ± 3.35 μmol L−1). Screening of the antiplasmodial activities of UT harmiquins against erythrocytic stages of the Plasmodium life cycle identified CQ-based UT harmiquine 12 as a novel antiplasmodial hit because it displayed low IC50 values in the submicromolar range against CQ-sensitive and resistant strains (IC50 0.06 ± 0.01, and 0.19 ± 0.02 μmol L−1, respectively), and exhibited high selectivity against Plasmodium, compared to mammalian cells (SI = 92).

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins

Faculty of Pharmacy and Biochemistry Department of Medicinal Chemistry

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or...

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins

Published Online: Dec 26, 2023

Page range: 537 - 558

Accepted: Jun 09, 2023

DOI: https://doi.org/10.2478/acph-2023-0035

Keywords
chloroquine, mefloquine, β-carboline, harmine, anti-plasmodial activity, antiproliferative activity

© 2023 Kristina Pavić et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins

Published Online: Dec 26, 2023

Page range: 537 - 558

Accepted: Jun 09, 2023

DOI: https://doi.org/10.2478/acph-2023-0035

Keywordschloroquine, mefloquine, β-carboline, harmine, anti-plasmodial activity, antiproliferative activity

© 2023 Kristina Pavić et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
chloroquine, mefloquine, β-carboline, harmine, anti-plasmodial activity, antiproliferative activity