Generating a Peptide Library Using the Repeats of Amino Acid Scaffolds Created by Sliding the Framework of a 7-mer Human Chemerin Segment and Discovery of Potent Antibacterial and Antimycobacterial Peptides DOI

Sariyah Akhtar,

Mohd Mustkim Ansari,

Rahul Dev Verma

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

The quest for new approaches generating novel bioactive designer proteins/peptides has continued with their success in various biomedical applications. Previously, we designed a 14-mer α-helical peptide antimicrobial and antimycobacterial activities by employing tandem repeat of the 7-mer, "KVLGRLV" human chemerin segment. Herein, devised method "sliding framework" this segment to create amino acid scaffolds varying sizes sequences explored design library antibacterial activities. By utilizing 2 7 repeats these 6-residue scaffolds, synthesized 30 peptides 10–16 residue lengths. Thus, identified AMPs α-helical, β-sheet, random coil structures, membrane-destabilizing, intracellular modes action, 9 them showed therapeutic indices between 100 750. Three two nine vivo antitubercular efficacies against Escherichia coli ATCC 25922 Mycobacterium bovis BCG infections, respectively, mouse model.

Язык: Английский

Pd/NBE-Catalyzed One-Pot Modular Synthesis of Tetrahydro-γ-carbolines DOI

Cuifeng Huang,

Wenlin Zhang, Ying Liu

и другие.

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Tetrahydro-γ-carbolines are especially outstanding fused heterocyclic ring systems possessing significant biological activities in the central nervous system. Here, using commercially available NBE derivatives (NBEs), we report an efficient protocol for one-pot modular synthesis of 4-substituted tetrahydro-γ-carbolines via Catellani/aza-Michael addition cascade from easily 3-iodo-1-tosyl-1H-indole, aziridines and olefins. This approach exhibits a wide substrate scope, good yields, scalability, potential extension toward Mebhydroline analogues.

Язык: Английский

Процитировано

0

A new computational cross-structure-activity relationship (C-SAR) approach applies to a selective HDAC6 inhibitor dataset for accelerated structure development DOI
Shaymaa E. Kassab

Computers in Biology and Medicine, Год журнала: 2025, Номер 192, С. 110169 - 110169

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0

Reversing TGF-β1-induced fibrotic phenotype in human lung fibroblasts using a PROTAC tool derived from an indoline-based HDAC6 inhibitor DOI Creative Commons
Ilaria Cursaro, Valerio Ciccone, Valeria Tudino

и другие.

European Journal of Medicinal Chemistry Reports, Год журнала: 2025, Номер unknown, С. 100276 - 100276

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0

Unlocking the Potential of Histone Deacetylase Inhibitors in Combatting Age-Related Retinal Degenerative Diseases DOI
Bo Liu, Minglu Wang,

Ning Pu

и другие.

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102788 - 102788

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0

Spirotetrahydroisoquinoline-Based Histone Deacetylase Inhibitors as New Antifibrotic Agents: Biological Evaluation in Human Fibroblasts from Bronchoalveolar Lavages of Idiopathic Pulmonary Fibrosis Patients DOI Creative Commons
Anna Fontana, Laura Bergantini, Gabriele Carullo

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 8(2), С. 380 - 393

Опубликована: Ноя. 12, 2024

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease typified by progressive fibrosing phenotype. IPF has been associated with aberrant HDAC activity, particularly HDAC6. Combining synthetic and modeling studies, new family of spirotetrahydroisoquinoline-capped histone deacetylase inhibitors 5a–o was developed. These analogues were prepared via the three-component Castagnoli–Cushman reaction (CCR) as key step. Structure–activity relationship (SAR) studies identified 5n (fibrostat) preferential HDAC6 inhibitor suitable degree selectivity compared to HDAC1, HDAC3, HDAC5, HDAC8, HDAC10, HDAC11. able negatively modulate expression fibrotic markers, fibronectin collagen 1, in fibroblasts derived from bronchoalveolar lavages patients. In another ex vivo human model, reduced affected 1 vimentin, latter being invasiveness. Finally, fibrostat did not show toxicity rat-perfused heart zebrafish larvae.

Язык: Английский

Процитировано

1

Generating a Peptide Library Using the Repeats of Amino Acid Scaffolds Created by Sliding the Framework of a 7-mer Human Chemerin Segment and Discovery of Potent Antibacterial and Antimycobacterial Peptides DOI

Sariyah Akhtar,

Mohd Mustkim Ansari,

Rahul Dev Verma

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

The quest for new approaches generating novel bioactive designer proteins/peptides has continued with their success in various biomedical applications. Previously, we designed a 14-mer α-helical peptide antimicrobial and antimycobacterial activities by employing tandem repeat of the 7-mer, "KVLGRLV" human chemerin segment. Herein, devised method "sliding framework" this segment to create amino acid scaffolds varying sizes sequences explored design library antibacterial activities. By utilizing 2 7 repeats these 6-residue scaffolds, synthesized 30 peptides 10–16 residue lengths. Thus, identified AMPs α-helical, β-sheet, random coil structures, membrane-destabilizing, intracellular modes action, 9 them showed therapeutic indices between 100 750. Three two nine vivo antitubercular efficacies against Escherichia coli ATCC 25922 Mycobacterium bovis BCG infections, respectively, mouse model.

Язык: Английский

Процитировано

1