Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore
(1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)<sub>2</sub> is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-s...
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MDPI AG
2021-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/23/7321 |
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| author | Sirine Jaber Veronica Nemska Ivan Iliev Elena Ivanova Tsvetelina Foteva Nelly Georgieva Ivan Givechev Emilia Naydenova Veronika Karadjova Dancho Danalev |
| author_facet | Sirine Jaber Veronica Nemska Ivan Iliev Elena Ivanova Tsvetelina Foteva Nelly Georgieva Ivan Givechev Emilia Naydenova Veronika Karadjova Dancho Danalev |
| author_sort | Sirine Jaber |
| collection | DOAJ |
| description | (1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)<sub>2</sub> is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)<sub>2</sub>-NH<sub>2</sub>. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)<sub>2</sub>-NH<sub>2</sub> and Caf-(KLAKLAK)<sub>2</sub>-NH<sub>2</sub>. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLβ-AKLβ-AK)<sub>2</sub>-NH<sub>2</sub> containing β-Ala in its structures exhibited good antimicrobial activity against <i>Escherichia coli</i> K12 407 and <i>Bacillus subtilis</i> 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents. |
| first_indexed | 2024-03-10T04:47:46Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T04:47:46Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d0e4992db759419e90a89c5fbbf8bfa52023-11-23T02:50:44ZengMDPI AGMolecules1420-30492021-12-012623732110.3390/molecules26237321Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second PharmacophoreSirine Jaber0Veronica Nemska1Ivan Iliev2Elena Ivanova3Tsvetelina Foteva4Nelly Georgieva5Ivan Givechev6Emilia Naydenova7Veronika Karadjova8Dancho Danalev9University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaUniversity of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 25 A, 1113 Sofia, BulgariaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 25 A, 1113 Sofia, BulgariaUniversity of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaUniversity of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaTesting Center Global Test Ltd., 31 Krushovski vrah Street, 1618 Sofia, BulgariaUniversity of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaUniversity of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaUniversity of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, Bulgaria(1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)<sub>2</sub> is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)<sub>2</sub>-NH<sub>2</sub>. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)<sub>2</sub>-NH<sub>2</sub> and Caf-(KLAKLAK)<sub>2</sub>-NH<sub>2</sub>. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLβ-AKLβ-AK)<sub>2</sub>-NH<sub>2</sub> containing β-Ala in its structures exhibited good antimicrobial activity against <i>Escherichia coli</i> K12 407 and <i>Bacillus subtilis</i> 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents.https://www.mdpi.com/1420-3049/26/23/7321(KLAKLAK)<sub>2</sub>antitumor peptides1,8-naphthalimidecaffeic acidunnatural amino acids |
| spellingShingle | Sirine Jaber Veronica Nemska Ivan Iliev Elena Ivanova Tsvetelina Foteva Nelly Georgieva Ivan Givechev Emilia Naydenova Veronika Karadjova Dancho Danalev Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore Molecules (KLAKLAK)<sub>2</sub> antitumor peptides 1,8-naphthalimide caffeic acid unnatural amino acids |
| title | Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore |
| title_full | Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore |
| title_fullStr | Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore |
| title_full_unstemmed | Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore |
| title_short | Synthesis and Biological Studies on (KLAKLAK)<sub>2</sub>-NH<sub>2</sub> Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore |
| title_sort | synthesis and biological studies on klaklak sub 2 sub nh sub 2 sub analog containing unnatural amino acid β ala and conjugates with second pharmacophore |
| topic | (KLAKLAK)<sub>2</sub> antitumor peptides 1,8-naphthalimide caffeic acid unnatural amino acids |
| url | https://www.mdpi.com/1420-3049/26/23/7321 |
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