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

Abstract

A series of 1-substituted-1H-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 ([Formula: see text]) 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 ([Formula: see text]) 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. 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.

Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents

“…These results may indicate strong correlation between antibacterial activity and lipophilic properties of the tested antibacterial agents. This observation stays in agreement with a general principle that antibacterial and antiproliferative activities of fluoroquinolones strongly depends on lipophilic profile, which condition their diffusion into bacterial [42,43] and human cancer cells [44,45]. In this context, increase in the overall lipophilic character of a quinolone derivative usually involves introduction of a bulky group at the N-4 position of piperazine, or more generally, at the C-7 position of the parent drug [42].…”

Impact of the functionalized tetrazole ring on the electrochemical behavior and biological activities of novel nickel (II) complexes with a series of tetrazole derivatives

“…The electron withdrawing effect of the pivaloyl group situated in position 1 of L 3 and L 4 ligands increases the potency. While compounds L 5 and L 6 contain in position 1 the methyl group, an electron donating group, found to weaken the antibacterial activity [87]. This result could be predicted by the DFT calculations.…”

Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

“…These hybrids exhibited promising in vitro antiproliferative activities when investigated against SiHA human cervical cancer cell line, MDA-MB-235 human adenocarcinoma, and PANC-1 pancreatic cancer cell line using the sulforhodamine B (SRB) assay method. Compounds 72 and 73 gave the highest activities among these analogs and higher than the reference, tamoxifen against SiHA and MDA-MB-231 cell lines with GI50 values, 0.07, 0.09, 0.06, 0.08, 0.12, and 0.24 μM, respectively [106].…”