Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes

Arif Iftikhar Khan (1) , Shahzad Nazir (1) , Aaqib Ullah (1) , Muhammad Nadeem Ul Haque (1) , Rukesh Maharjan (1) , Shabana U Simjee (1) , Hamza Olleik (2) , Elise Courvoisier-Dezord (2) , Marc Maresca (2) , Farzana Shaheen (1)

1 University of Karachi
2 ISM2 - Institut des Sciences Moléculaires de Marseille

As the technologies for peptide synthesis and development continue to mature, antimicrobial peptides (AMPs) are being widely studied as significant contributors in medicinal chemistry research. Furthermore, the advancement in the synthesis of dendrimers' design makes dendrimers wonderful nanostructures with distinguishing properties. This study foregrounds a temporin SHa analog, [G10a]-SHa, and its dendrimers as globular macromolecules possessing anticancer and antibacterial activities. These architectures of temporin SHa, named as [G10a]-SHa, its dendrimeric analogs [G10a] 2-SHa and [G10a] 3-SHa, and [G10a] 2-SHa conjugated with a polymer molecule, i.e., Jeff-[G10a] 2-SHa, were synthesized, purified on RP-HPLC and UPLC and fully characterized by mass, NMR spectroscopic techniques, circular dichroism, ultraviolet, infrared, dynamic light scattering, and atomic force microscopic studies. In pH-and temperature-dependent studies, all of the peptide dendrimers were found to be stable in the temperature range up to 40-60 • C and pH values in the range of 6-12. Biological-activity studies showed these peptide dendrimers possessed improved antibacterial activity against different strains of both Gram-positive and Gram-negative strains. Together, these dendrimers also possessed potent selective antiproliferative activity against human cancer cells originating from different organs (breast, lung, prostate, pancreas, and liver). The high hemolytic activity of [G10a] 2-SHa and [G10a] 3-SHa dendrimers, however, limits their use for topical treatment, such as in the case of skin infection. On the contrary, the antibacterial and anticancer activities of Jeff-[G10a] 2-SHa, associated with its low hemolytic action, make it potentially suitable for systemic treatment.

Mots clés: Temporin SHa; D-alanine; antimicrobial peptide; Rink amide resin; dendrimer; antibacterial; anticancer

Domaines: Chimie thérapeutique

Arif Iftikhar Khan, Shahzad Nazir, Aaqib Ullah, Muhammad Nadeem Ul Haque, Rukesh Maharjan, et al.. Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes. Biomolecules, 2022, 12 (6), pp.770. ⟨10.3390/biom12060770⟩. ⟨hal-04029563⟩