Synthesis, Characterization, In Vitro Anticancer Potentiality, and Antimicrobial Activities of Novel Peptide–Glycyrrhetinic-Acid-Based Derivatives

Abstract

Glycyrrhetinic acid (GA) is one of many interesting pentacyclic triterpenoids showing significant anticancer activity by triggering apoptosis in tumor cell lines. This study deals with the design and synthesis of new glycyrrhetinic acid (GA)–amino acid peptides and peptide ester derivatives. The structures of the new derivatives were established through various spectral and microanalytical data. The novel compounds were screened for their in vitro cytotoxic activity. The evaluation results showed that the new peptides produced promising cytotoxic activity against the human breast MCF-7 cancer cell line while comparing to doxorubicin. On the other hand, only compounds 3, 5, and 7 produced potent activity against human colon HCT-116 cancer cell line. The human liver cancer (HepG-2) cell line represented a higher sensitivity to peptide 7 (IC50; 3.30 μg/mL), while it appeared insensitive to the rest of the tested peptides. Furthermore, compounds 1, 3, and 5 exhibited a promising safety profile against human normal skin fibroblasts cell line BJ-1. In order to investigate the mode of action, compound 5 was selected as a representative example to study its in vitro effect against the apoptotic parameters and Bax/BCL-2/p53/caspase-7/caspase-3/tubulin, and DNA fragmentation to investigate beta (TUBb). Additionally, all the new analogues were subjected to antimicrobial assay against a panel of Gram-positive and Gram-negative bacteria and the yeast candida Albicans. All the tested GA analogues 1–8 exhibited more antibacterial effect against Micrococcus Luteus than gentamicin, but they exhibited moderate antimicrobial activity against the tested bacterial and yeast strains. Molecular docking studies were also simulated for compound 5 to give better rationalization and put insight to the features of its structure.

New pyrazolopyridine and pyrazolothiazole-based compounds as anti-proliferative agents targeting c-Met kinase inhibition: design, synthesis, biological evaluation, and computational studies

“…All apoptotic processes, such as cell shrinkage, chromatin condensation, and DNA fragmentation, depend on caspase-3. 68,69…”

Novel 1,2,3-Triazole-Coumarin Hybrid Glycosides and Their Tetrazolyl Analogues: Design, Anticancer Evaluation and Molecular Docking Targeting EGFR, VEGFR-2 and CDK-2

“…The Mitochondria apoptotic pathway involves mitochondrial outer membrane permeabilization or MOMP, followed by cytochrome-c release into the cytosol, leading to the activation of pro-caspase-9, which in turn cleaves and activates the executioner caspases-3 and -7 [ 67 ]. The executioner caspase is known by its ability to effectively kill the cell within minutes through the parallel cleavage of hundreds of different substrates.…”

“…The precoated micro-ELISA plate with an antibody specific to Caspase-3 was applied using the Human Caspase-3 ELISA Kit from Invitrogen INC. Catalog # KHO1091 (96 tests) (542 Flynn Road, Camarillo, CA, USA) according to the manufacturer’s instructions [ 67 ].…”

Alkaloid-Metabolomics & DNA profiles: Role-bioassay-guided differentiation process of Six Annona cultivated in Egypt on anti-cancer therapy

“…The method was carried out according to that of [27]. The sensitivity of different cell lines (HepG2, Caco, HCT, MCF7, T47D; ATCC, USA) cell lines were taken from the Vacsera (Giza, Egypt) [28] to the extracts determined by the SRB assay. SRB is a bright pink amino xanthene dye with two sulfonic groups.…”