Medicinal Chemistry Research Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Molecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Pharmacol Ther. 2021 Sep;225:107860. doi: 10.1016/j.pharmthera.2021.107860. Epub 2021 Apr 22.
Heterocyclic scaffolds are widely utilized for drug design by taking into account the molecular structure of therapeutic targets that are related to a broad spectrum of ailments, including tumors. Such compounds display various covalent and non-covalent interactions with the specific residues of the target proteins while causing their inhibition. There is a substantial number of heterocyclic compounds approved for cancer treatment, and these compounds function by interacting with different therapeutic targets involved in tumorogenesis. In this review, we trace and emphasize the privileged heterocyclic pharmacophores that have immense potency against several essential chemotherapeutic tumor targets: microtubules, kinases and carbonic anhydrases. Potent compounds currently undergoing pre-clinical and clinical studies have also been assessed for ascertaining the effective class of chemical scaffolds that have significant therapeutic potential against multiple malignancies. In addition, we also describe briefly the role of heterocyclic compounds in various chemotherapy regimens. The optimized molecular hybridization of delineated motifs may result in the discovery of more active anticancer therapeutics and circumvent the development of resistance by specific targets in the future.
杂环骨架被广泛用于药物设计，考虑到与广泛疾病相关的治疗靶点的分子结构，包括肿瘤。这些化合物与靶蛋白的特定残基显示出各种共价和非共价相互作用，同时导致其抑制。有大量杂环化合物被批准用于癌症治疗，这些化合物通过与肿瘤发生中涉及的不同治疗靶点相互作用发挥作用。在这篇综述中，我们追溯并强调了具有针对几种重要化学治疗肿瘤靶点的巨大潜力的优势杂环药效团：微管、激酶和碳酸酐酶。目前正在进行临床前和临床研究的有效化合物也进行了评估，以确定对多种恶性肿瘤具有重要治疗潜力的有效化学支架类别。此外，我们还简要描述了杂环化合物在各种化疗方案中的作用。所描述的基序的优化分子杂交可能导致发现更有效的抗癌治疗方法，并在未来避免特定靶标产生耐药性。
