Medicinal Chemistry - Online First
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Expanding Therapeutic Horizons with Indazole-Based Compounds: A Review of Anticancer, Antimicrobial, and Neuroprotective Applications
Authors: Pooja Dinkar Bhane and Sarita Suryabhan PawarAvailable online: 18 April 2025More LessIndazole-based compounds have recently developed and physiologically evaluated as diverse agents for antibacterial, anticancer, anti-inflammatory, anti-obesity, and neurological therapies. This review highlights these advancements. Through molecular docking and experimental tests, scientists have created distinct indazole analogs that exhibit significant inhibitory effects on various biological targets, including 1,2,3-triazolyl-indazoles, carbothioamides, and carboxamides. Key compounds have demonstrated strong bactericidal and antifungal properties against microbes such as S. epidermidis, P. aeruginosa, E. coli, and C. albicans; their effectiveness was enhanced by halogenated and electron-withdrawing substituents. In models including positive HER2 breast cancer and hepatocellular tumors, indazole derivatives have shown efficacy against targets such as CDK2, EGFR, c-Met, HSP90, and VEGFR2 in oncology, resulting in successful anticancer responses. The pharmacokinetics, solubility, and specificity of these compounds have been further improved through structural alterations, such as piperazine ring modifications and C-terminal changes.
Additionally, the LRRK2 antagonist MLi-2 demonstrated remarkable efficacy in treating neurodegenerative diseases, while indazole-5-carboxamides exhibited a strong affinity for monoamine oxidases, potentially offering new therapeutic options for Parkinson's disease. Inhibition of COX-2 and FGFR resulted in anti-inflammatory effects, with minimal off-target damage observed in vivo. Collectively, our findings underscore the therapeutic versatility of indazole frameworks across various disease pathways, suggesting their potential for developing innovative treatments for cancer, infections, metabolic disorders, and neurological conditions.
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Bioactive Compounds from Myrica esculenta: Antioxidant Insights and Docking Studies on H+K+-ATPase and H2 Receptor Targets
Authors: Rashmi Pathak and Phool ChandraAvailable online: 04 February 2025More LessBackgroundMyrica esculenta (Myricaceae) are common in the Indian Himalayas. Traditional medicine uses it to treat chronic bronchitis, inflammation, stomach ulcers, anaemia, diarrhoea, asthma, and ear, throat, and nose disorders. Its varied medicinal benefits are recognised in the ayurvedic pharmacopoeia.
AimIsolation of Bioactive Compounds from M. esculenta: Assessment of Antioxidant Activity and Molecular Docking Studies Targeting the H+K+-ATPase enzyme and H2 Receptor
Material and MethodsThe fruit of the Myrica esculenta plant was extracted. The total phenolic and total flavonoid content of the extract were determined. Following column chromatography, two phytoconstituents were identified by mass spectroscopy, FTIR, and NMR. The antioxidant activity of phytoconstituents was evaluated using the DPPH Scavenging Assay, Reactive Nitrogen Oxide Scavenging Assay, and Hydroxyl Free Radical Scavenging Assay. Then, molecular docking studies were performed against the H+K+-ATPase enzyme and H2 Receptor.
ResultsThe research successfully extracted methanolic extract from M. esculenta by maceration, which yielded rich in flavonoids and phenolic content and isolated compounds using column chromatography, which was further characterized to be myricetin and catechin using Mass spectroscopy, FTIR, and NMR. The further evaluation of the antioxidant activity of compounds demonstrated significant activity with IC50 value indicating strong free radical scavenging activity. Molecular docking studies were performed against the H+K+-ATPase enzyme and H2 Receptor, revealing that both the compounds exhibit high binding affinity and favorable interactions with key sites.
ConclusionThe findings suggest that the isolated compounds myricetin and catechin possess potential antioxidant activity and could be a potential therapeutic target for the H+K+-ATPase enzyme and H2 Receptor.
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Effective Synthesis of Dopamine Dimer
Authors: Zhou Dejun, Zhang Yuying, Liu Xiaoyue and Zheng HuachuanAvailable online: 23 January 2025More LessBackgroundDopamine (1) is a commonly used vasopressor, primarily employed to treat various types of shock, congestive heart failure, and acute renal failure. Dopamine dimer (2) is an impurity generated during the production process of dopamine raw materials or the metabolism of dopamine drugs themselves.
MethodsThis article presents an effective method for synthesizing dopamine dimer through the condensation of methyl 3,4-dimethoxyphenyl acetate (4) and 3,4-dimethoxyphenylethyl amine (5), followed by reduction and demethylation.
ResultsThe product was synthesized from easily accessible raw materials, achieving a total yield of 48% over five steps.
ConclusionThis synthesis method is simple and beneficial for pharmaceutical companies to adopt and implement.
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Advances in Structural Types and Pharmacochemistry of CDK12 Inhibitors
Authors: Dan Wang, Ming-tao Xia, Jia-xin Yan, Ling Yu and Shuai LiAvailable online: 21 January 2025More LessCyclin-Dependent Kinase (CDK) 12 is a member of the 20-membered CDK family (CDK1-20) and plays a vital role in regulating gene transcription, mRNA splicing, translation, cell cycle, and repair of DNA damage. CDK12 is an emerging therapeutic target due to its role in regulating the transcription of DNA Damage Response (DDR) genes in Cyclin-Dependent Kinase (CDK). However, the development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13. So far, no CDK12 inhibitors approved by the US FDA have been found, and more novel CDK12 inhibitors have been reported for the treatment of prostate cancer, breast cancer, ovarian cancer, lung adenocarcinoma, stomach cancer, cervical cancer, etc. This review has attempted to summarize the structural characteristics and biological activities of various novel CDK12 inhibitors reported since 2020. Meanwhile, we collated and analyzed the reported CDK12 inhibitors from the perspective of structure, summarized the current clinical application potential of CDK12 inhibitors, and further analyzed their current challenges and future development trends.
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