Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Chemistry Department (Biochemistry Branch), Faculty of Science, Cairo University, Giza, Egypt.
Mini Rev Med Chem. 2019;19(8):657-670. doi: 10.2174/1389557518666181017162459.
Isobutyrohydrazonoyl bromide 1 was used as a precursor for the synthesis of 4-imino-3-isopropyl-1-(4-nitrophenyl)-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine 4, which was converted into hydrazino derivative 5 by heating with hydrazine hydrate at reflux. Hydrazino, as well as imino-amino derivatives, underwent condensation and cyclization reactions to give pyrazolo[ 3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives, respectively.
Antimicrobial studies are performed using two-gram positive bacteria and two-gram negative bacteria.
Data revealed that compound 9a is the most promising antibacterial agent with high efficiency (low MIC value (48 μg/ml)). The cytotoxic assay was investigated for in vitro antitumor screening against Caucasian breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2 and colon carcinoma HCT-116 cell lines.
The results are compared with doxorubicin standard anticancer drugs as well as normal cell lines like MCF10 and MCF12. Molecular docking was carried out for the highest potent compound 8c with the binding site of dihydrofolate reductase enzyme DHFR PDB:ID (1DLS).
异丁酰肼溴化物 1 被用作合成 4-亚氨基-3-异丙基-1-(4-硝基苯基)-1,4-二氢-5H-吡唑并[3,4-d]嘧啶-5-胺 4 的前体，将其与水合肼在回流下加热转化为肼基衍生物 5。肼基以及亚氨基-氨基衍生物分别进行缩合和环化反应，得到吡唑并[3,4-d]嘧啶和吡唑并[4,3-e][1,2,4]三唑并[3,4-c]嘧啶衍生物。
使用两种革兰氏阳性菌和两种革兰氏阴性菌进行抗菌研究。
数据显示，化合物 9a 是最有前途的抗菌剂，具有高效（低 MIC 值（48 μg/ml））。对体外抗肿瘤筛选进行了细胞毒性测定，针对高加索人乳腺癌 MCF7、肝癌 HepG2 和结肠癌细胞 HCT-116 细胞系。
将结果与阿霉素标准抗癌药物以及正常细胞系 MCF10 和 MCF12 进行了比较。对最高效的化合物 8c 进行了分子对接，与二氢叶酸还原酶 DHFR PDB：ID（1DLS）的结合位点进行了对接。
