Natural Products as a Source of Inspiration for Novel Inhibitors of Advanced Glycation Endproducts (AGEs) Formation

Protein glycation, a post-translational modification found in biological systems, is often associated with a core defect in glucose metabolism. In particular, advanced glycation endproducts are complex heterogeneous sugar-derived protein modifications implicated in the progression of pathological conditions such as atherosclerosis, diabetic complications, skin diseases, rheumatism, hypertension, and neurodegenerative diseases. Undoubtedly, there is the need to expand the knowledge about antiglycation agents that can offer a therapeutic approach in preventing and treating health issues of high social and economic importance. Although various compounds have been under consideration, little data from clinical trials are available, and there is a lack of approved and registered antiglycation agents. Next to the search for novel synthetic advanced glycation endproduct inhibitors, more and more the efforts of scientists are focusing on researching antiglycation compounds from natural origin. The main purpose of this review is to provide a thorough overview of the state of scientific knowledge in the field of natural products from plant origin (e.g., extracts and pure compounds) as inhibitors of advanced glycation endproduct formation in the period between 1990 and 2019. Moreover, the objectives of the summary also include basic chemistry of AGEs formation and classification, pathophysiological significance of AGEs, mechanisms for inhibiting AGEs formation, and examples of several synthetic anti-AGEs drugs.

Skrining Virtual dan Elusidasi Moda Ikatan Senyawa dalam Bawang Putih (Allium Sativum L.) sebagai Penghambat Reseptor Advanced Glycation end Products

Diabetes memiliki dampak jangka panjang seperti aterosklerosis, nefropati, dan retinopati yang disebabkan oleh pembentukan Advanced Glycation End Products (AGEs). Penelitian secara in vitro pada ekstrak bawang putih (Allium sativum L.) terhadap aktivitas penghambatan pembentukan AGEs telah banyak dilakukan, namun belum diketahui mekanisme penghambatan dan senyawa apa yang berperan aktif dalam aktivitas penghambatan tersebut. Penelitian ini bertujuan untuk melakukan skrining virtual senyawa – senyawa dalam bawang putih (Allium sativum L.) yang aktif menghambat reseptor Advanced Glycation Endproduct sehingga senyawa aktif bisa dipertimbangkan sebagai kandidat senyawa obat. Metode yang digunakan adalah molecular docking dengan software PLANTS, YASARA, MarvinSketch, dan visualisasi ikatan senyawa uji pada asam amino reseptor menggunakan PyMOL, piridoksamin dan aminoguanidin digunakan sebagai kontrol positif inhibitor AGEs. Hasil docking 24 senyawa uji diperoleh tujuh senyawa yang aktif menghambat reseptor 3B75.pdb dan lima senyawa aktif menghambat reseptor 3O3U.pdb. Kandidat senyawa obat terdiri dari senyawa organosulfur, fenol dan flavonoid. Senyawa Ɣ-glutamil-sistein, E-ajoene, Nα-(1-Deoksi-Dfructosa-1-YL)-L-Arginin, Kaempferol-3-o-β-D-glukopiranosa, Iso-rhamnetin-3-o-β-D-glukopiranosa merupakan senyawa – senyawa dalam bawang putih yang memiliki kemampuan menghambat baik reseptor 3B75 maupun 3O3U dengan aktivitas yang lebih baik dari piridoksamin dan aminoguanidin.

Chemical Reactivity Theory and Empirical Bioactivity Scores as Computational Peptidology Alternative Tools for the Study of Two Anticancer Peptides of Marine Origin

This work presents an account of the reactivity behavior of the anticancer marine drugs, Soblidotin and Tasidotin, based on the calculation of the global and local descriptors resulting from Chemical Reactivity Theory (CRT), also known as Conceptual DFT, for their consideration as a useful complement to approximations based on Molecular Docking. The information on the global and local reactivity descriptors of the Soblidotin and Tasidotin molecules, obtained through our proposed methodology, may be used for the design of new pharmaceutical analogs by relying on the chemical interactions between these peptides and their protein-type biological receptors. It can be concluded that the CRT approximation to the global and local chemical reactivity, based on the descriptors, can provide interesting information for the consideration of both molecules as potential therapeutic drugs. This is complemented by a study on Advanced Glycation Endproduct (AGE) inhibition, by comparison with the usual molecular systems considered for the task, as a re-purposing study. Finally, the bioactivity scores for Soblidotin and Tasidotin are predicted through an empirical procedure, based on comparison with molecular structures with well-known pharmacological properties.

Impact of free Nε-carboxymethyllysine, its precursor glyoxal and AGE-modified BSA on serotonin release from human parietal cells in culture

The advanced glycation endproduct CML, often encountered in a Western diet, increases serotonin release from cultured parietal cells, while a protein-linked AGE showed the opposite effect.

Screening and identification of inhibitors of advanced glycation endproduct formation from microalgal extracts

Identification of fucoxanthin as a key inhibitor of AGE formation in marine microalgae.