{"title":"Stereoisomerism in Chemistry and Drug Development: Optical, Geometrical, and Conformational Isomers.","authors":"Shivani Chawla, Rishikesh Gupta, Sudhanshu Kumar Jha, Shamim, Sarfraj Kashid, Keshav Taruneshwar Jha","doi":"10.2174/0115734064366389250923044201","DOIUrl":"https://doi.org/10.2174/0115734064366389250923044201","url":null,"abstract":"<p><p>Stereoisomerism in addition to conformational, geometrical, and optical isomerism, has considerable effects on the stability, reactivity, and functioning of molecules. Therefore, the objective of this article is to review the recent developments and research on stereoisomerism, including its consequences in various branches of science. The energetics and stability of conformational isomerism, which depict the concept of cis-trans and E/Z configurations of geometric isomerism, elucidate the molecular behavior and the efficacy of drugs, also discussed. The consequence of stereochemistry on pharmacology and drug design is elucidated by optical isomerism in terms of chirality and enantiomorphic effects. To exemplify the use of stereoisomerism in drug development, this review, offers wide case studies of NSAIDs, anticancer drugs, and antibiotic drugs. In this Article, the phenomenon of stereoisomerism is also primarily discussed concerning biomolecules such as proteins, carbohydrates, lipids, and nucleic acids. Recent advances in comparison operations include computer-aided drug design, advances in personalized medicine, and new therapies such as DNA and peptide drugs, including their possible impacts on the business and natural world. The primary aim of the review is to thoroughly investigate and examine stereoisomerism and its wide-ranging implications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232956","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}
Medicinal ChemistryPub Date : 2025-09-17DOI: 10.2174/0115734064390136250818063436
Eya Caridad, Timoteo Delgado-Maldonado, Diana V Navarrete-Carriola, Lenci K Vázquez-Jiménez, Eyra Ortiz-Perez, Alma D Paz-González, Ignacio Martinez, Bertha Espinoza, Gildardo Rivera
{"title":"<i>In Vitro</i> Evaluation of <i>p</i>-Toluenesulfonyl Hydrazones as Anti-<i>Trypanosoma cruzi</i> and Leishmanicidal Agents.","authors":"Eya Caridad, Timoteo Delgado-Maldonado, Diana V Navarrete-Carriola, Lenci K Vázquez-Jiménez, Eyra Ortiz-Perez, Alma D Paz-González, Ignacio Martinez, Bertha Espinoza, Gildardo Rivera","doi":"10.2174/0115734064390136250818063436","DOIUrl":"https://doi.org/10.2174/0115734064390136250818063436","url":null,"abstract":"<p><strong>Introduction: </strong>Neglected tropical diseases (NTDs), such as Chagas disease (CD) and Cutaneous Leishmaniasis (CL), are significant global health concerns. The limited number of treatments and their severe adverse effects worsen the situation. Therefore, the development of molecules as a new pharmacological alternative is necessary. This work aimed to obtain new p- Toluenesulfonyl hydrazones derivatives to determine their potential antiparasitic activity against <i>Trypanosoma cruzi (T. cruzi)</i> and <i>Leishmania mexicana (L. mexicana)</i>.</p><p><strong>Methods: </strong>Compounds were synthesized by condensing p-Toluenesulfonyl hydrazide with aromatic aldehydes using acetic acid as a catalyst. All compounds were structurally elucidated using infrared (IR) spectroscopy, proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR), and Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry (UPLCMS). The Queretaro (Qro) strain of <i>T. cruzi</i> and the M379 strain of <i>L. mexicana</i> were used for <i>in vitro</i> assays.</p><p><strong>Results: </strong>Compound pT-21 (IC<sub>50</sub>= 49.6 μM) was the most active agent against the <i>T. cruzi</i> Qro strain. Meanwhile, compounds pT-15 and pT-21 inhibited the proliferation of <i>L. mexicana</i> promastigotes with an IC<sub>50</sub> value of 59.2 and 13.8 μM, respectively. In addition, these compounds had low cytotoxic effects against Vero cell lines (CC<sub>50</sub> values >100 μM).</p><p><strong>Discussion: </strong>In this study, compound pT-21 inhibited the proliferation of <i>T. cruzi</i> and <i>L. mexicana in vitro</i>. Its activity is attributed to the reactivity of the 5-nitrofuran ring (present in other drugs such as nifurtimox). Future research could focus on identifying the pharmacological target of compound pT-21 to facilitate rational drug design and enhance its potency against these parasites.</p><p><strong>Conclusion: </strong>In summary, these results show that p-Toluenesulfonyl hydrazones serve as a scaffold to aid in the development of potent and selective agents against <i>T. cruzi</i> and <i>L. mexicana</i>.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086467","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}
Medicinal ChemistryPub Date : 2025-09-16DOI: 10.2174/0115734064385863250815045326
Sabeen Arshad, Aneela Maalik, Wajid Rehman, Yousaf Khan, Hina Sarfraz, Liaqat Rasheed, Mohammed B Hawsawi, Mustafa S Alluhaibi, Majed Alharbi
{"title":"Discovery of Novel 1,3,4-oxadiazole-based Inhibitors Against Urease and Diabetes: Design, Synthesis, SAR, Biological, and Molecular Docking Screening.","authors":"Sabeen Arshad, Aneela Maalik, Wajid Rehman, Yousaf Khan, Hina Sarfraz, Liaqat Rasheed, Mohammed B Hawsawi, Mustafa S Alluhaibi, Majed Alharbi","doi":"10.2174/0115734064385863250815045326","DOIUrl":"https://doi.org/10.2174/0115734064385863250815045326","url":null,"abstract":"<p><strong>Introduction: </strong>Heterocyclic compounds bearing oxygen and nitrogen atoms are key pharmacophores in modern drug design. Among them, 1,3,4-oxadiazoles are notable for their diverse biological activities, including anti-inflammatory, anticancer, antidiabetic, antibacterial, and enzyme inhibitory effects. This study focuses on the synthesis and evaluation of indazole-based 1,3,4-oxadiazole-benzenesulfonothioate hybrids as potential therapeutic agents.</p><p><strong>Method: </strong>A multistep synthetic route was employed to develop a series of eighteen (18) analogues. The synthetic strategy involved the formation of methyl 5-methyl-1H-indazole-3-carboxylate, conversion to carbohydrazide, cyclization with CS<sub>2</sub>, and final coupling with substituted benzenesulfonyl chlorides to yield the target hybrids (1-18).</p><p><strong>Results: </strong>The urease inhibition potential of scaffolds ranged from IC<sub>50</sub> = 17.88 ± 0.36 to 37.98 ± 0.80 μM as compared to the standard drug thiourea (IC<sub>50</sub> = 29.45 ± 0.76 μM). The exceptional urease and α-glucosidase activity was shown by scaffolds (4, 7, 9, 11) due to the presence of electron- withdrawing groups (-F, NO<sub>2</sub>, and Cl). In comparison, the α-glucosidase inhibition potential shown by all the scaffolds was in the range (IC<sub>50</sub> = 3.19 ± 0.27 - 12.24 ± 1.33 μM). Compound-9 showed promising inhibitory potential against urease, with an IC<sub>50</sub> = 17.90 ± 0.30 μM, and α- glucosidase (IC<sub>50</sub> = 3.19 ± 0.27 μM), both indicating minimum IC<sub>50</sub> values.</p><p><strong>Discussion: </strong>The enhanced activity of compounds bearing electron-withdrawing groups (F, NO2, Cl) supports their role in modulating enzyme inhibition. In silico molecular docking further confirmed strong binding affinities with the active sites of target enzymes, correlating well with the experimental results.</p><p><strong>Conclusion: </strong>The synthesized 1,3,4-oxadiazole derivatives demonstrate promising dual inhibitory activity against urease and α-glucosidase, suggesting their potential as lead compounds in the treatment of gastric infections and diabetes. This study contributes to the ongoing development of multifunctional therapeutic agents with improved efficacy and selectivity.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080324","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}
Medicinal ChemistryPub Date : 2025-09-11DOI: 10.2174/0115734064378178250815080012
Kalyani A Dalvi, Sarita S Pawar
{"title":"Recent Advances in Synthetic Pathways and Therapeutic Potential of Acridine and Acridone Derivatives.","authors":"Kalyani A Dalvi, Sarita S Pawar","doi":"10.2174/0115734064378178250815080012","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","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}
Medicinal ChemistryPub Date : 2025-09-11DOI: 10.2174/0115734064385944250826074612
Kunal G Raut, Anuruddha R Chabukswar, Priyanka S Waghmare, Swati C Jagdale, Onkar G Kachi, Hari R Pawar
{"title":"Exploring Recent Advances in the Pharmacological Activities of Pyrazole Compounds: A Comprehensive Review.","authors":"Kunal G Raut, Anuruddha R Chabukswar, Priyanka S Waghmare, Swati C Jagdale, Onkar G Kachi, Hari R Pawar","doi":"10.2174/0115734064385944250826074612","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","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}
Medicinal ChemistryPub Date : 2025-09-09DOI: 10.2174/0115734064398347250815061230
Abrar Hussain, Sayeda Sania Seher, Shahzaib Akhter, Khurram Shahzad, Muhammad Arfan, Kyong-Cheol Ko, Sang Hyun Park
{"title":"Recent Advances in the Biological Profiles of Fluorine-Containing Pyridine and its Derivatives: A Brief Overview.","authors":"Abrar Hussain, Sayeda Sania Seher, Shahzaib Akhter, Khurram Shahzad, Muhammad Arfan, Kyong-Cheol Ko, Sang Hyun Park","doi":"10.2174/0115734064398347250815061230","DOIUrl":"https://doi.org/10.2174/0115734064398347250815061230","url":null,"abstract":"<p><p>Fluorine-containing pyridine derivatives have emerged as pivotal structures in modern drug discovery due to their unique physicochemical properties and diverse pharmacological activities. The incorporation of fluorine into pyridine-based scaffolds enhances drug potency, selectivity, metabolic stability, and Pharmacokinetics (PK) of these compounds, making them highly attractive for therapeutic development. These derivatives have been integrated into numerous Food and Drug Administration (FDA)-approved drugs, underscoring their importance in medicinal chemistry. This review systematically compiles recent advances in the pharmacological applications of fluorine-containing pyridine derivatives, focusing on their anticancer, antidiabetic, antioxidant, and anti-Alzheimer's activities. By exploring the Structure-Activity Relationship (SAR) and mechanisms of action, this review provides valuable insights for the design and development of novel biologically active compounds. This comprehensive analysis aims to inspire new directions in drug discovery and highlight the therapeutic potential of fluorine- containing pyridine derivatives.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065150","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}
Medicinal ChemistryPub Date : 2025-09-01DOI: 10.2174/0115734064381790250722071316
Panagiotis Theodosis-Nobelos, Eleni A Rekka
{"title":"Pluripotent Cinnamic Acid and Valproic Acid Hybrid Molecules Designed as Strong Anti-inflammatory and Anti-hyperlipidemic Compounds.","authors":"Panagiotis Theodosis-Nobelos, Eleni A Rekka","doi":"10.2174/0115734064381790250722071316","DOIUrl":"https://doi.org/10.2174/0115734064381790250722071316","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammation and oxidative stress are considered main pathophysiological factors for neuronal and cardiovascular diseases, also leading to the impairment of main cellular metabolic pathways. Promotion of hyperlipidemia is also the result of inflammatory and oxidative (ROS production) processes. Additionally, compounds of medicinal interest like valproic and caffeic acids and amino acids like proline and tyrosine have shown antiinflammatory and cellular protective potency.</p><p><strong>Methods: </strong>In the present study, amides of L-tyrosine, L-proline, and L-cysteine, and an ester of cinnamyl alcohol were synthesized by conjugation with caffeic acid, valproic acid, or (E)-3- (3,4-dimethoxyphenyl)acrylic acid (cinnamic acid derivative). This design aimed to explore the multiple activities of novel compounds, via the combination of structures related to the desired biological characteristics. The synthesized compounds were tested for their effects on oxidative stress in vitro and on acute inflammation and hyperlipidemia in vivo.</p><p><strong>Results: </strong>The synthesized compounds decreased carrageenan-induced rat paw oedema up to 69% (the most active compound 6), and 49% for compound 2, an amide of valproic acid with L-tyrosine. Several compounds were effective antioxidants, with radical scavenging and lipid peroxidation inhibitory activity. Additionally, the synthesized molecules significantly decreased the plasma lipidemic markers in tyloxapol-induced hyperlipidemic rats. They decreased plasma triglycerides and total cholesterol up to 53% and 78% (compound 1), and LDL-cholesterol up to 69% (compound 5).</p><p><strong>Discussion: </strong>The anti-inflammatory activity of the derivatives was equal to or much higher than that of ibuprofen and tolfenamic acid, two widely applied NSAIDs (nonsteroidal antiinflammatory drugs), whilst compound 2 was 3.3 times more active than valproic acid, with the latter being tested at four times higher dose. Concerning the antioxidant activity, several compounds were comparable to the strong antioxidant Trolox, and the effect on cholesterol levels for all the derivatives was comparable to or equal to simvastatin [a 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase inhibitor].</p><p><strong>Conclusion: </strong>The multiple activities of the synthesized compounds may serve for the manipulation of conditions involving inflammation and lipid deregulation, or the further optimization and production of compounds towards these ailments.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000927","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":"Advances in Medicinal Chemistry of Fused and Substituted Piperazines: Unlocking their Potential as Anticancer Agents.","authors":"Saumya Singh, Rajnish Kumar, Shrishti Tripathi, Salahuddin, Avijit Mazumder","doi":"10.2174/0115734064383459250806115629","DOIUrl":"https://doi.org/10.2174/0115734064383459250806115629","url":null,"abstract":"<p><p>Cancer is an abnormal growth of normal cells and has become a global healthcare concern. The availability of safer anticancer drugs with exceptional selectivity for healthy cells and high efficacy against various forms of cancer remains a significant challenge. Therefore, there is a need to develop target-specific and safer anticancer drugs. In medicinal chemistry, heterocyclic compounds play a crucial role by exhibiting diverse biological activities. Specifically, nitrogen-containing heterocyclic compounds are widely studied due to their diverse activities. The piperazine moiety serves as the building block for several molecules and is reported to have the ability to inhibit the cell cycle (G1/S phase), suppress angiogenesis, and interact with DNA. Piperazine also exhibits a flexible binding feature that enables it to interact with a range of biological targets, making it effective against various types of cancer. As there is a continuous need for an anticancer drug with improved efficacy and fewer side effects, piperazine derivatives are attracting the attention of researchers. This review highlights recent methods for the synthesis of fused and substituted piperazines, their structure-activity relationships, and their interactions with biological targets or receptors as anticancer agents. Thus, the presented review will be helpful to medicinal chemists in designing anticancer molecules that incorporate piperazines.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959510","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}
Medicinal ChemistryPub Date : 2025-08-22DOI: 10.2174/0115734064389466250805052834
Mahalakshmi C S Parepalli, Rajitha Galla
{"title":"Design, Synthesis, Biological Evaluation, and <i>In Silico</i> Studies of Tetrazole Derivatives as Potential Cytotoxic Agents.","authors":"Mahalakshmi C S Parepalli, Rajitha Galla","doi":"10.2174/0115734064389466250805052834","DOIUrl":"https://doi.org/10.2174/0115734064389466250805052834","url":null,"abstract":"<p><strong>Introduction: </strong>Despite significant progress in cancer treatment, the need for new anticancer agents remains critical. Current research efforts are directed toward discovering novel compounds that exhibit potent cytotoxic activity while minimizing adverse effects. Thus, tetrazole derivatives have gained attention due to their potential biological activities, including anticancer effects.</p><p><strong>Methods: </strong>A series of tetrazole derivatives (6a-l) were synthesized via α-keto halogenation of 2,4-difluoroacetophenone, followed by cyclization, nucleophilic substitution, and subsequent coupling with various aryl carboxylic acids. The synthesized compounds were characterized using spectroscopic techniques, including <sup>13</sup>C NMR, <sup>1</sup>H NMR, FT-IR, and HRMS. Their cytotoxic potential was assessed through an MTT assay across four human cancer cell lines. Other cytotoxic evaluations included apoptosis induction, cell cycle analysis, and EGFR-TK inhibition assays. Additionally, molecular docking studies were conducted to explore binding interactions, and in silico ADME predictions were performed to assess pharmacokinetic properties.</p><p><strong>Results: </strong>The results obtained by the MTT assay indicated that compound 6d demonstrated significant cytotoxicity against A549 (lung cancer) cell lines, with an IC50 value of 2.74 μM, compared to doxorubicin (IC<sub>50</sub> = 3.87 μM). Furthermore, cell cycle analysis and apoptosis suggested that 6d arrested the cell cycle in the S phase and triggered apoptosis in A549 cells. Docking studies and EGFR-TK inhibition assay proposed that 6l had good binding affinity towards EGFR enzyme and acts as a potential inhibitor (IC<sub>50</sub> 0.099 μM). The ADME analysis demonstrated favourable molecular properties, including acceptable lipophilicity, strong absorption, and high oral bioavailability.</p><p><strong>Discussion: </strong>The synthesized tetrazole derivatives exhibited notable anticancer potential, with compound 6d inducing S-phase arrest and apoptosis in lung cancer cells, and 6l demonstrating strong EGFR inhibition. These biological effects were further supported by docking studies and favorable ADME profiles, providing mechanistic insight into their activity.</p><p><strong>Conclusion: </strong>These findings indicate that the synthesized derivatives offer a promising approach for developing innovative and effective cancer therapies.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959559","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}