Medicinal Chemistry最新文献

{"title":"Discovery of the PARP1 Inhibitors from Natural Compounds Using Structure-Based Virtual Screening and Bioactivity Evaluation.","authors":"Dabo Pan, Yaxuan Huang, Dewen Jiang, Xiaojie Jin, Mingkai Wu, Jianjun Luo, Yonghao Zhang","doi":"10.2174/0115734064350048241121110017","DOIUrl":"10.2174/0115734064350048241121110017","url":null,"abstract":"<p><strong>Background: </strong>PARP1 (poly ADP-ribose polymerase 1, also known as ADPRT1) plays a significant role in DNA repair and has become an attractive target for treating PARP1-related diseases, such as cancer.</p><p><strong>Objective: </strong>This study aimed to discover inhibitors targeting PARP1 from the phytochemicals of Huangbai (Phellodendron chinense Schneid.), Baixianpi (<i>Dictamnus dasycarpus</i> Turcz.), and Shechuangzi (<i>Cnidium monnieri</i> (L.) Spreng.).</p><p><strong>Methods: </strong>The chemical compositions of Huangbai, Baixianpi, and Shechuangzi were extracted from the HERB database. Next, a combination of molecular docking and PARP1 enzyme assay was used to identify PARP1 inhibitors from these chemical components. Finally, molecular dynamics simulation and binding free energy calculation were used to explore the detailed interaction mode of these inhibitors with PARP1.</p><p><strong>Results: </strong>A total of 507 chemical constituents of Huangbai, Baixianpi, and Shechuangzi were collected from the HERB database. Four potential PARP1 inhibitors were screened based on molecular docking and PARP1 enzyme assay. Demethyleneberberine exhibited strong PARP1 inhibitory activity with an IC₅₀ value of 2.0 ± 0.8 μM. The IC₅₀ values of the inhibitory activities of 8-hydroxy dictanmnine, meranzin hydrate, and osthol on PARP1 ranged from 44 μM to 76 μM. Molecular dynamics simulation and binding free energy calculation suggested that the nonpolar interaction energies of HIS862, GLY863, TYR889, TYR896, PHE897, and TYR907 played a primary role in the binding of inhibitors to PARP1.</p><p><strong>Conclusion: </strong>Integrating molecular simulation and bioactivity testing was found to be an effective approach for the rapid discovery of targeted PARP1 inhibitors. Demethyleneberberine demonstrated strong PRAP1 inhibitory activity and has a good prospect for development.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"57-66"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Warriors: Design and Synthesis of Dual-Acting Schiff-Based Threaded 1,2,3-Triazole Hybrids for Potent Antineoplastic and Anti-Mycobacterial Activities.","authors":"Vinayak Walhekar, Raghavendra Kulkarni, Mohana Vamsi Nuli, Anil Kumar Garige, Dharmesh Deore, Ritesh Pawar, Ashwini Patil, Bhikshapathi Dvrn, Karajagi Santosh, Ravindra Kulkarni","doi":"10.2174/0115734064318062250206104355","DOIUrl":"10.2174/0115734064318062250206104355","url":null,"abstract":"<p><strong>Objective: </strong>In the pursuit of identifying divergent scaffolds for potential anticancer and anti-mycobacterial agents, a novel series of Schiff-based threaded 1,2,3-triazoles was designed and synthesized.</p><p><strong>Methods: </strong>In this study, novel Schiff-based threaded 1,2,3-triazoles have been meticulously crafted and synthesized. Chemical structures of the synthesized molecules were confirmed by ¹H NMR, ¹³C NMR and Mass spectra. Synthetic analogs were further evaluated for their antiproliferative, antitubercular and antimicrobial potentials by in vitro assays.</p><p><strong>Results: </strong>The in vitro anti-tumor (anti-proliferative) evaluation on HT29 cancer cells revealed that compounds 8b and 8h exhibited remarkable inhibitory activity with IC50 values of 25 ± 0.8 and 24 ± 0.9 μM. In the context of anti-mycobacterial analysis, compound 8c demonstrated promising activity (6.25 μM) against <i>Mycobacterium tuberculosis</i> H37Rv. Moreover, compounds 8d and 8e displayed equipotent antimicrobial potential (3.12 μM) comparable to Ciprofloxacin against both <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. Molecular docking studies unveiled that 8c exhibited robust binding within the active pocket of carbonic anhydrase XII (docking energy -8.4 kcal/mol) and demonstrated a promising docking profile with β-ketoacyl ACP synthase I (docking energy - 9.5 kcal/mol) in the enzyme's binding pocket.</p><p><strong>Conclusion: </strong>Structure-activity relationship (SAR) analysis identified three pivotal pharmacophores; 1,2,3-triazole, aromatic ring system (substituted with halogens and -NO₂), and imine functionalities as crucial for the development of dual inhibitors targeting cancer and tuberculosis, showcasing an outstanding <i>in silico</i> ADMET profile. Therefore, these compounds merit consideration as noteworthy pharmacological lead molecules in the realm of cancer and tuberculosis drug discovery and development.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"99-111"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrimidine-Based Compounds in Tuberculosis Management: A Review of their Biological and Medicinal Importance.","authors":"Deepshikha Singh, Vikram Singh, Afrasim Moin, Manu Gangadhar, Bistuvalli Chandrashekarappa Revanasiddappa, Sheshagiri R Dixit","doi":"10.2174/0115734064364791250314135438","DOIUrl":"10.2174/0115734064364791250314135438","url":null,"abstract":"<p><p>Pyrimidine derivatives are a class of chemically and biologically active heterocyclic compounds promising for developing anti-tubercular, anti-viral, anti-malarial, anti-inflammatory, and enzyme-inhibiting drugs. To cure TB, scientists were driven to establish novel pyrimidine derivatives. The main objective of the current review is to identify and develop new pyrimidine moiety- containing derivatives that have been assessed for their structure-activity relationship (SAR). Several drug-resistant MTB infections have emerged and spread worldwide, which has rendered first-line medication ineffective. It is crucial to develop new anti-TB drugs that are extremely effective against both drug-sensitive and drug-resistant TB. The development of pyrimidine therapeutic methods will thus benefit from the current review. Three medications-GSK-286, TBA-7371, and SPR-720 are now undergoing clinical testing. This study aims to emphasize the structural variety of anti-tuberculosis pyrimidine-containing compounds by providing an overview of current developments in drug discovery investigations.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"127-138"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Pyridine-Based Schemes: A Comprehensive Review on their Synthesis and Therapeutic Applications.","authors":"Amruta M Balikai, M R Pradeep Kumar, Kalirajan Rajagopal, Mohammed Ali Alshehri, Safia Obaidur Rab, Mohamed H Nafady, Talha Bin Emran","doi":"10.2174/0115734064343054250108152240","DOIUrl":"10.2174/0115734064343054250108152240","url":null,"abstract":"<p><p>Pyridine and its derivatives are six-membered aromatic rings containing nitrogen, which are abundant in nature and indispensable in studying heterocyclic chemistry. They constitute significant chemical substances with numerous applications. The application of pyridine derivatives by incorporating metals in modern medicine is growing in relevance. Due to their convenient parallelization and various testing capabilities in the chemical domain, pyridine derivatives have attracted increased interest in the treatment of various disease states. This review aims to systematically evaluate and highlight the recent advancements in the synthesis (conventional, synthetic, and green approach) and biological activities of metal-based pyridine derivatives, including antioxidant, antimicrobial, and antitumor activities, while identifying promising candidates for further drug development. By consolidating all this knowledge underlying their biological effects, this review aims to pave the way for future research endeavors and encourage the exploration of pyridine derivatives as viable therapeutic agents across a diverse array of medical applications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"1-29"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Synthetic Pathways and Therapeutic Potential of Acridine and Acridone Derivatives.","authors":"Kalyani Asraji Dalvi, Sarita Suryabhan Pawar","doi":"10.2174/0115734064378178250815080012","DOIUrl":"10.2174/0115734064378178250815080012","url":null,"abstract":"<p><p>Cancer, bacterial, parasitic, viral, and neurological diseases like Alzheimer's continue to pose serious health risks around the world. We need new therapeutic agents that are more targeted, effective, and safer. Because of their wide range of biological actions, acridine and its derivatives have become increasingly popular among the numerous intriguing chemical classes. Over time, several synthetic analogs of these substances have shown great promise, exhibiting noteworthy antitumor properties (e.g., N-(2-(dimethylamino) ethyl) acridine-4-carboxamide (DACA) and triazole acridone (C-1305)), as well as strong antimicrobial (e.g., 4-amino-N-[amino(imino) methyl]-benzene sulphonamide), antiviral (e.g., derivatives of acridine sulphonamide), and anti- Alzheimer's (e.g., Citrusinine-I) properties. These substances have therapeutic potential, but side effects frequently prevent them from being used in clinical settings. This review discusses all the new developments in acridine and acridone derivatives since 2024. It focuses on how they are made and might be used in medicine. By shedding light on these innovations, the study aims to offer a fresh perspective on their role in shaping the future of medicinal chemistry and drug development. This work's main goal is to investigate and evaluate the most current progress in the synthesis as well as biological uses concerning derivatives of acridine along with acridone, especially those that have been published after 2024. The target of the study is to demonstrate the compounds' medicinal perspective by highlighting their antiviral, anticancer, antibacterial, and anti-Alzheimer effects. Furthermore, the research aims to tackle the difficulties related to their adverse effects, offering valuable perspectives for the creation of safer and more efficient medications in the field of medicinal chemistry in the future.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"242-267"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Recent Advances in the Pharmacological Activities of Pyrazole Compounds: A Comprehensive Review.","authors":"Kunal Ganesh Raut, Anuruddha Rajaram Chabukswar, Priyanka Sanjay Waghmare, Swati Changdeo Jagdale, Onkar Gangaram Kachi, Hari Ragho Pawar","doi":"10.2174/0115734064385944250826074612","DOIUrl":"10.2174/0115734064385944250826074612","url":null,"abstract":"<p><p>Pyrazole-based compounds have gained considerable attention in recent years due to their diverse and potent pharmacological properties. This review provides an up-to-date examination of the therapeutic potential of various substituted pyrazole derivatives, highlighting their roles in combating diseases such as cancer, tuberculosis, fungal and viral infections, inflammation, and others. Unlike previous reviews, this article emphasises newly reported analogues with significant bioactivity and structure-activity relationships (SAR), which may pave the way for future drug development. The novelty of this work lies in its integrated perspective that bridges medicinal chemistry innovations with therapeutic relevance, providing researchers with a valuable resource for designing next-generation drug candidates based on the pyrazole scaffold.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"268-288"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin-Based Virtual Screening Identifies Inhibitors of SARS-CoV-2 Spike Protein and ACE2 Receptor Binding.","authors":"Timoteo Delgado-Maldonado, Luis D Gonzalez-Morales, Gilberto Vargas-Salas, Guadalupe Rojas-Verde, Eyra Ortíz-Pérez, Alma D Paz-Gonzalez, Gildardo Rivera","doi":"10.2174/0115734064371154250414064157","DOIUrl":"10.2174/0115734064371154250414064157","url":null,"abstract":"<p><strong>Background: </strong>To date, COVID-19 has caused over 772 million cases, with approximately 7 million deaths, according to the World Health Organization. Therefore, there is a need to develop new drugs to address the challenges posed by this disease.</p><p><strong>Objective: </strong>To propose new antiviral agents based on the natural product curcumin as potential protein-protein interaction inhibitors between the SARS-CoV-2 spike receptor binding domain (RBD) and the ACE2 receptor.</p><p><strong>Methods: </strong>A curcumin-based virtual screening was performed (Tanimoto coefficient= 0.9), and molecular docking analysis were carried out using the RBD as a receptor. Molecular dynamics (MD) using GROMACS were conducted for 120 ns. The SwissADME server was used to predict pharmacokinetics properties. To validate predictions, an in vitro enzyme assay measuring the relative inhibition of the interaction between the RBD and the ACE2 receptor was performed.</p><p><strong>Results: </strong>More than 1300 ligands were evaluated through molecular docking. The docking results were analyzed, and the ligands were classified according to their score and profile of interactions with residues of the RBD of the SARS-CoV-2 S glycoprotein. The top ten with the best scores and interactions were selected to verify the commercial availability. The lead compound Cu-1 demonstrated significant interactions with the RBD and stability in MD simulations, was acquired and evaluated in vitro. Compound Cu-1 inhibited 36 ± 0.7% the interaction between the SARSCoV- 2 spike and the ACE2 receptor. In addition, Cu-1 was shown to have an acceptable druglikeness and pharmacokinetic profile.</p><p><strong>Conclusion: </strong>Curcumin provides a scaffold for identifying novel compounds with potential antiviral activity. Further studies on compound Cu-1 could yield on optimizing its structure to increase activity targeting the RBD of the S glycoprotein.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"139-149"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaffold Hopping and Optimization of Thiazole Hybrids as Selective PIN1 Inhibitors: A Computational Study.","authors":"Meeramol C Chellappan, Soumya Vasu, Shriraam Mahadevan, Muthu Kumaradoss Kathiravan, Saravanan Jayaraman, Soniya Naik, Knolin K Thachil","doi":"10.2174/0115734064376657250416071044","DOIUrl":"10.2174/0115734064376657250416071044","url":null,"abstract":"<p><strong>Background: </strong>Protein Interacting with NIMA1 (PIN1) is a distinct enzyme, known as a peptidyl-prolyl cis-trans isomerase (PPIase), which catalyzes the cis-trans isomerization of amide bonds in proteins containing phosphoserine/threonine-proline (pSer/Thr-Pro) motifs, presenting a unique therapeutic opportunity for addressing multiple disorders.</p><p><strong>Methods: </strong>A series of 140 thiazole compounds were created using the shape similarity technique with the intention of discovering effective PIN1 inhibitors with a new scaffold. The designed compounds were docked into the enzyme's ATP binding site, and the binding free energies for all docked conformations were calculated. The compounds were evaluated for their ADMET and drug-likeness properties. Following the identification of top candidates, molecular dynamics simulations were conducted to investigate the binding dynamics of the highest-scoring compound.</p><p><strong>Results: </strong>Based on computational findings, sixteen compounds were identified as potential PIN1 inhibitors. Among the sixteen compounds, four (S8Ba, S8Bb, S8Bc, and S8Bd) exhibited the most favorable ADMET profiles and robust interactions with key PIN1 residues. Molecular dynamics simulations confirmed that S8Ba and S8Bc exhibited the most promising activity over 100ns.</p><p><strong>Conclusion: </strong>The results corroborated the docking outcomes, validating the selected hits as potential PIN1 inhibitors. This breakthrough could influence the development of therapeutic leads for combating diabetes, cancer, and Alzheimer's disease.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"174-192"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of Phosphatidylinositol-specific Phospholipase C wit h <i>Myo</i>-inositol Scaffold.","authors":"Christian Bierkamp, Walburga Hanekamp, Christoph Arenz, Matthias Lehr","doi":"10.2174/0115734064384345250415073648","DOIUrl":"10.2174/0115734064384345250415073648","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes catalyze the conversion of phosphatidylinositol-4,5-bisphosphate into the second messengers diacylglycerol and inositol- 1,4,5-trisphosphate, both of which play crucial roles in regulating biochemical processes. Despite the wellestablished link between elevated PI-PLC activity and pathophysiological conditions, no PI-PLC inhibitors are currently in clinical development. Moreover, existing inhibitors demonstrate only limited potency.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Due to the structural similarity with known inhibitors with a &lt;i&gt;myo&lt;/i&gt;-inositol backbone, DL-1-Ododecylsulfonyl- &lt;i&gt;myo&lt;/i&gt;-inositol-3,5-bisphosphate, designated as acid sphingomyelinase inhibitor, and derivatives thereof should be tested for inhibition of PI-PLC activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The newly synthesized compounds were evaluated for their ability to inhibit PI-PLC activity in porcine platelet lysate and porcine brain homogenate, as well as their inhibitory potency against the recombinant isoenzymes PLCγ1 and PLCγ2. The assay measured the release of diacylglycerol from L-α- phosphatidylinositol using HPLC coupled with MS detection. Furthermore, the specificity of selected compounds was assessed by determining their inhibitory potency against other surface-active enzymes through HPLC-based assays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;It was found that DL-1-O-dodecylsulfonyl-myo-inositol-3,5-bisphosphate inhibits PI-PLC activity at micromolar concentrations. However, its maximum achievable inhibitory effect was limited to approximately 70%. Through structural modifications, inhibitors were developed that led to near complete inhibition of PIPLC activity. The study also revealed that the alleged PI-PLC inhibitor U73122, still frequently cited in the literature to demonstrate PI-PLC involvement in biochemical processes, is unsuitable for this purpose. Consistent with observations by others, its inhibitory activity in bionucleophile-containing cell or tissue preparations was found to be significantly lower than its activity against purified PI-PLC enzymes. Additionally, U73122 was shown to inhibit other enzymes, such as cytosolic phospholipase A&lt;sub&gt;2&lt;/sub&gt;α, fatty acid amide hydrolase, and monoacylglycerol lipase, which, like PI-PLC, metabolize lipophilic substrates. In contrast, the newly developed &lt;i&gt;myo&lt;/i&gt;-inositol derivatives exhibited reduced sensitivity to bionucleophiles and significantly improved selectivity against the tested surface-active enzymes compared to U73122.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;New compounds exhibiting significant inhibitory activity against PI-PLC have been identified. The findings could prove valuable in the development of clinically applicable PI-PLC inhibitors, particularly for the treatment of cancer. Additionally, the &lt;i&gt;myo&lt;/i&gt;-inositol derivatives developed demonstrated greater suitability for studying PI-PLC's role in physiological pr","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"150-173"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrazole and Pyrazoline-Based EGFR TK Inhibitors: A Review Study Emphasizing Structure-Activity Relationship (SAR).","authors":"Shruti Mittal, Ozair Alam, Lakshay Singh, Kannan, Aasma Shakuli, Vishal Mathur, Mukund Jha, Anam Ilyas, Shaheen Ali, Mohd Javed Naim, Sana Tanweer","doi":"10.2174/0115734064373755250409165138","DOIUrl":"10.2174/0115734064373755250409165138","url":null,"abstract":"<p><p>Unusual cell growth patterns, metastasis (the spread of tumors to other parts of the body), and potential death are all hallmarks of cancer. Research in oncology clearly shows that abnormalities in EGFR expression directly contribute to uncontrolled cell growth and division, resulting in the development of carcinomas. People with cancer have developed resistance due to mutations in several EGFR-associated genes. Tyrosine kinase inhibitors (TKIs) and other cancer treatments must, therefore, undergo continuous improvement. Currently, fourth-generation tyrosine kinase inhibitors (TKIs) that act allosterically against the C797S mutation are the most widely used class of medications that target EGFR mutations. To help researchers better understand how to optimize pyrazole and pyrazoline-based derivatives as antiproliferative agents, this review summarises the work done in the last fifteen years on different anti-cancer agents representing 31 most potential compounds along with their activity characteristics, with a particular emphasis on the structure-activity relationship (SAR) of possible pyrazole and pyrazoline derivatives as EGFR tyrosine kinase inhibitors.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"313-346"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}