Asu Busra Temizer

Antioxidants neutralize free radicals to reduce oxidative stress and cellular damage, preventing various chronic diseases. In this study, the antioxidant activities of novel 5‐(trifluoromethyl)‐3 H ‐spiro[1,3‐benzothiazole‐2,3′‐indol]‐2′(1′ H )‐ones ( 4a–h ), along with the spirocyclic 2‐indolinones ( 4i–m and 5a–n ) previously synthesized by our group, were investigated for the first time, to find a multi‐modal antioxidant and to understand the impact of the trifluoromethyl group located at the 5‐position of the benzothiazole on antioxidant activity. For this purpose, the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH•) free radical scavenging, superoxide anion scavenging, ABTS ^•+ radical cation scavenging, trolox equivalent antioxidant capacity, ferric ion reduction antioxidant potential (FRAP), and lipid peroxidation (TBARs) assays were carried out. The cytotoxic effects of compounds ( 4g , 4h , 4i , 4j , 4l , 5a , 5b , and 5h) , which showed promising in vitro antioxidant activity in at least two in vitro tests, were investigated in healthy human fibroblast (HFF‐1) cells. The effects of non‐toxic doses of these compounds on intracellular reactive oxygen species were also evaluated. As a result, it was determined that compound 4l (R ₁ = 5‐F and R ₂ = H) exhibited greater radical scavenging activity than the other compounds tested. The IC ₅₀ of compound 4l was 74.13 µM while compound 4g (R ₁ = 5‐Cl‐7‐CH ₃ and R ₂ = H) was non‐toxic (IC ₅₀ > 200 μM). Compounds 4e (R ₁ = 5‐Cl and R ₂ = H) and 4f (R ₁ = 7‐Br and R ₂ = H), exhibited higher lipid peroxidation inhibitory activity than α‐tocopherol in vitro; however, the difference was not statistically significant.

2‐Indolinone is a versatile scaffold that has been the central moiety in the structure of various drugs. Since the introduction of sunitinib malate, 2‐indolinones have been a principal pharmacophoric building block in many drug discovery studies, especially in the last few years. Compounds bearing the 2‐indolinone ring system have shown various therapeutic effects, including but not limited to, antidiabetic, antioxidant, anti‐inflammatory, anti‐HIV, antimicrobial, antipsychotic, antiparkinson, and anticancer activities. Considering that cancer is among the major global causes of death, the antiproliferative activities of these compounds have been the goal of numerous studies. The present review presents an overview of the approaches and advances made during the last eight years (2017–2024) regarding the development of 2‐indolinone derivatives within the field of anticancer drug discovery. The derivates gathered herein are classified according to the therapeutic target of the developed compounds, and notable structure‐activity relationships as well as significant molecular docking interactions with the target enzymes have been highlighted in each instance. Accordingly, special attention has been paid to reporting derivatives with superior antiproliferative and enzymatic inhibitory effects that have emerged as lead compounds within each respective study.

As a member of heterocyclic compounds, indole possesses a diverse set of biological activities. Studies on the structure-activity relationship of 2-indolinones have shown that they are important bioactive compounds in the field of pharmaceutical chemistry. Isatin and structures bearing isatin scaffold are derivatives of indole, which have shown to be of biological and pharmacological significance. This review focuses on different ways of obtaining compounds containing isatin structure, considering both earlier and recent methods of synthesis. The syntheses given herein were grouped into three categories, syntheses using anilines as their starting substance, synthetic methods based on the oxidation of indoles, and finally, due to the extensive research going on 5-substituted isatins and their possible pharmacological efficacy, pathways for synthesizing 5-amino and 5-sulfamoylisatins were gathered to underline the importance of 2-indolinone and isatin derivatives as prospective therapeutic compounds in current and future drug discovery studies.

Machine learning models have found numerous successful applications in computational drug discovery. A large body of these models represents molecules as sequences since molecular sequences are easily available, simple, and informative. The sequence‐based models often segment molecular sequences into pieces called chemical words, analogous to the words that make up sentences in human languages, and then apply advanced natural language processing techniques for tasks such as de novo drug design, property prediction, and binding affinity prediction. However, the chemical characteristics and significance of these building blocks, chemical words, remain unexplored. To address this gap, we employ data‐driven SMILES tokenization techniques such as Byte Pair Encoding, WordPiece, and Unigram to identify chemical words and compare the resulting vocabularies. To understand the chemical significance of these words, we build a language‐inspired pipeline that treats high affinity ligands of protein targets as documents and selects key chemical words making up those ligands based on tf–idf weighting. The experiments on multiple protein–ligand affinity datasets show that despite differences in words, lengths, and validity among the vocabularies generated by different subword tokenization algorithms, the identified key chemical words exhibit similarity. Further, we conduct case studies on a number of target to analyze the impact of key chemical words on binding. We find that these key chemical words are specific to protein targets and correspond to known pharmacophores and functional groups. Our approach elucidates chemical properties of the words identified by machine learning models and can be used in drug discovery studies to determine significant chemical moieties.