Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Chem Biodivers. 2022 May;19(5):e202100956. doi: 10.1002/cbdv.202100956. Epub 2022 Apr 5.
In drug discovery, the hybridization of bioactive pharmacophores is a powerful tool for targeting enzymes involved in cancer and microbial cell growth. A combination of 1,3,4-oxadiazole and isobenzofuran may improve the antitumor and antimicrobial properties of the hybrid molecules. A series of hybrid molecules having 1,3,4-oxadiazole and isobenzofuran were synthesized and structural characterization was done by FT-IR, H-NMR, C-NMR, and mass spectrometry. Molecular docking studies were performed to investigate binding interactions of compounds with proteins (PDB NO: 2R3J and 1GII), and the results were consistent with in vitro anticancer data. All the synthesized compounds were tested for antimicrobial activity against S. aureus, E. faecalis (Gram-positive) and E. coli and P. aeruginosa (Gram-negative) bacterial strains. Among the synthesized compounds, 7a and 7b displayed good activity against the tested bacterial strains. Also, compounds were tested for their anti-tumor activity against breast cancer (MCF-7) and colon cancer (HCT-116) cell lines via SRB assay. In comparison to doxorubicin (1.14 μM), hybrids 7e (4.32 μM), 7f (4.15 μM), 7g (4.66 μM), and 7h (4.83 μM) demonstrated comparable IC value against the HCT 116 cell line.
在药物发现中，生物活性药效团的杂交是靶向参与癌症和微生物细胞生长的酶的有力工具。将 1,3,4-噁二唑和异苯并呋喃组合使用可能会提高杂交分子的抗肿瘤和抗菌特性。合成了一系列具有 1,3,4-噁二唑和异苯并呋喃的杂交分子，并通过 FT-IR、H-NMR、C-NMR 和质谱对其结构进行了表征。进行了分子对接研究以研究化合物与蛋白质（PDB NO：2R3J 和 1GII）的结合相互作用，结果与体外抗癌数据一致。所有合成的化合物均针对金黄色葡萄球菌、粪肠球菌（革兰氏阳性）和大肠杆菌和铜绿假单胞菌（革兰氏阴性）进行了抗菌活性测试。在合成的化合物中，7a 和 7b 对测试的细菌菌株表现出良好的活性。此外，还通过 SRB 测定法测试了化合物对乳腺癌（MCF-7）和结肠癌（HCT-116）细胞系的抗肿瘤活性。与多柔比星（1.14 μM）相比，杂种 7e（4.32 μM）、7f（4.15 μM）、7g（4.66 μM）和 7h（4.83 μM）对 HCT 116 细胞系的 IC 值相当。
