Synthesis, Cytotoxicity, Antimicrobial and Docking Simulation of Novel Pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c] pyrimidine Derivatives

Hamdi M Hassaneen; Fatma M Saleh; Tayseer A Abdallah; Magda F Mohamed; Yasmin Sh Mohamed; Enas M Awad; Ismail A Abdelhamid

doi:10.2174/1389557518666181017162459

Synthesis, Cytotoxicity, Antimicrobial and Docking Simulation of Novel Pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c] pyrimidine Derivatives

Mini Rev Med Chem. 2019;19(8):657-670. doi: 10.2174/1389557518666181017162459.

Authors

Hamdi M Hassaneen¹, Fatma M Saleh¹, Tayseer A Abdallah¹, Magda F Mohamed², Yasmin Sh Mohamed³, Enas M Awad⁴, Ismail A Abdelhamid¹

Affiliations

¹ Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
² Chemistry Department (Biochemistry Branch), Faculty of Science, Cairo University, Giza, Egypt.
³ National Organization for Drug Control and Research, Dokki, Giza, Egypt.
⁴ Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Cairo, Egypt.

PMID: 30332953
DOI: 10.2174/1389557518666181017162459

Abstract

Background: 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.

Method: Antimicrobial studies are performed using two-gram positive bacteria and two-gram negative bacteria.

Results: 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.

Conclusion: 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).

Keywords: DHFR; Modeling simulation; antibacterial activity; cytotoxicity; hydrazine hydrate; hydrazones; imino-amino..

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Drug Screening Assays, Antitumor
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Humans
Microbial Sensitivity Tests
Molecular Docking Simulation
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Spectrum Analysis / methods

Substances

Anti-Bacterial Agents
Antineoplastic Agents
Pyrazoles
Pyrimidines
pyrazolo(3,4-d)pyrimidine