Synthesis of novel tetrazole containing hybrid ciprofloxacin and pipemidic acid analogues and preliminary biological evaluation of their antibacterial and antiproliferative activity

• Published in: Molecular diversity 2018-02, Vol.22 (1), p.83-93
• Main Authors: Dileep, Kommula, Polepalli, Sowjanya, Jain, Nishant, Buddana, Sudheer Kumar, Prakasham, R. S., Murty, M. S. R.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bacteria - drug effects; Biochemistry; Biological activity; Biomedical and Life Sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Cervical cancer; Chemical compounds; Chemical synthesis; Ciprofloxacin - chemistry; Humans; Inhibition; Life Sciences; Microbial Sensitivity Tests; Molecular Structure; Organic Chemistry; Original Article; Pharmacy; Pipemidic Acid - chemistry; Polymer Sciences; Structure-Activity Relationship; Tetrazoles - chemical synthesis; Tetrazoles - chemistry; Tetrazoles - pharmacology
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-017-9795-y

A series of 1-substituted-1 H -tetrazole-5-thiol building blocks were synthesized and introduced to the N -4 piperazinyl group at C-7 position of the quinolone core, and these novel compounds ( 5a – g and 8a – g ) were screened for their antibacterial and antiproliferative activities. Bioactive assay studies manifested that most of new compounds exhibited significant antibacterial activity against the tested strains, including multi-drug-resistant MRSA in comparison with reference drugs ciprofloxacin, streptomycin B and pipemidic acid. Among the synthesized compounds, only ciprofloxacin ( 5a – g ) derivatives displayed significant activity ( MIC = 15.6 μ g / mL ) compared to reference drugs. In addition, these compounds were evaluated for their in vitro inhibition of human cancer cell lines viz human cervical carcinoma cell line (SiHA), breast adenocarcinoma (MDA-MB-235) and human pancreas carcinoma (PANC-1) cell lines by using the SRB assay method. Most of the target compounds showed broad potent growth inhibition activity ( GI 50 ≤ 0.1 μ M ) against all the tested cancer cell lines compared with reference drug. The most promising active compounds in this series were 5c , 5d , 8c , 8d and 8f endowed with excellent antiproliferative activity. Graphical abstract A new class of compounds was designed rationally by introducing tetrazole building block on N -4 piperazinyl group at C-7 position of quinolones core. The titled compounds were evaluated for their preliminary antibacterial and antiproliferative activities.