Synthesis and biological evaluation of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates
Autor: | Poola Sreelakshmi, Balam Satheesh Krishna, Sarva Santhisudha, Sudileti Murali, Gajjala Raghavendra Reddy, Chintha Venkataramaiah, Pasupuleti Visweswara Rao, Avula Vijaya Kumar Reddy, Vallela Swetha, Grigory Vasilievich Zyryanov, Chichili Devendhranath Reddy, Cirandur Suresh Reddy |
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Rok vydání: | 2022 |
Předmět: |
Male
Molecular Structure Dose-Response Relationship Drug Organic Chemistry Organophosphonates Prostatic Neoplasms Antineoplastic Agents Biochemistry Molecular Docking Simulation Structure-Activity Relationship Cell Line Tumor Drug Discovery Humans Drug Screening Assays Antitumor Molecular Biology Cell Proliferation |
Zdroj: | Bioorganic chemistry. 129 |
ISSN: | 1090-2120 |
Popis: | This study reports the design and synthesis of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates as potential antitumor agents against A549 (lung cancer), DU-145 (prostate cancer), PC-3 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer), cell lines evidenced from the in vitro antitumor studies performed by MTT assay (across 10-30 μM concentrations). The structural eminence of these synthesized molecules has emanated by designing the structural core by uniting the chromene, pyrimidine and phosphonate moieties into one, which has augmented their novelty and made them unreported. Further the deep structural activity relationship study investigations articulated that the title compounds are promising drug-like compounds and potential inhibitor of histidine amino acid residue present on the respective enzymatic proteins [3QJZ (A549), 3VHE (DU-145), 3V49 (PC-3), 3F81 (HeLa),amp; 3R7Q (MCF-7)] of the cell lines screened and are identified as responsible for the multi-faceted antitumor activities predicted in vitro. The obtained results were further supported by molecular docking studies, QSAR, ADMET, and bioactivity studies which have supported them as potential BBB penetrable molecules and proficient CNS active neuro-protective agents during drug delivery. |
Databáze: | OpenAIRE |
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