Design, synthesis and biological evaluation of novel pyrazole-based compounds as potential chemotherapeutic agents

Abstract

Aim: Design and synthesis of pyrazole-based chemotherapeutic agents. Materials & methods: A series of novel diphenyl pyrazole–chalcone derivatives were synthesized and assessed for their cytotoxic activities against 14 cancer cell lines and their antimicrobial activities against MRSA and Escherichia coli along with their safety using HSF normal cell line. Results & conclusion: Majority of the compounds showed moderate-to-significant anticancer activity with selective high percentage inhibition (>80%) against HNO-97 while being nontoxic toward normal cells. Compounds 6b and 6d were the most potent congeners with IC₅₀ of 10 and 10.56 μM respectively. The synthesized compounds exhibited moderate to potent antimicrobial activities. Interestingly, compound 6d exhibited a minimum inhibitory concentration of 15.7 μg/ml against MRSA; and a minimum inhibitory concentration of 7.8 μg/ml versus E. coli.

Summary points

Aim

• Design and synthesis of nontoxic pyrazole–chalcone hybrids as dual anticancer and antimicrobial agents.

Materials & methods

• A series of novel diphenyl pyrazole–chalcone derivatives were synthesized and evaluated for their cytotoxic activities against 14 cancer cell lines. All the synthesized compounds were further assessed for their antimicrobial activities against Gram-positive MRSA and Gram-negative Escherichia coli ATCC 25922. Finally, the synthesized compounds were further tested for their cytotoxicity against normal cell line HSF.

• Most of the compounds showed moderate to significant anticancer activity against the tested cancer cell lines with a selective high percentage inhibition (>80%) against HNO-97 at a concentration of 100 μg/ml. Compounds (6b and 6d) were the most potent congeners of the series with IC₅₀ of 10.5 and 10 μM, respectively.

• The synthesized compounds evinced moderate to potent antimicrobial activities against both the tested strains; MRSA and E coli; with superior activities against E. coli being two to eightfold more potent than the reference compound; Ciprofloxacin. Interestingly, compound 6d exhibited a moderate MIC of 15.7 μg/ml against MRSA; and a potent MIC of 7.8 μg/ml versus E. coli. All synthesized compounds demonstrated a good safety profile, as they were proven to be nontoxic toward normal cells.

Keywords: :

• anticancer
• antimicrobial
• E. coli
• MRSA
• nontoxic
• pyrazole chalcone

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17568919.2024.2347090

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.