Synthesis and biological evaluation of some 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones: antibacterial, DNA photocleavage, and anticancer activities.
In continuation of our efforts to find new biologically active agents, regioselective synthesis of a series of 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones 4a-k has been achieved under facile, extremely mild and greener reaction conditions with excellent yields. Moreover, one pot multicomponent reaction has also been reinvestigated under previously reported solvent conditions to prepare 4a-b and found that the reaction generates significant amount of side products. The chemical structures of 4a-k were established on the basis of a combined use of IR, NMR ((1)H, (13)C) spectroscopy, mass spectrometry and elemental analysis. All the compounds were evaluated for their antibacterial, DNA photocleavage and anticancer activities. Among all, 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-(naphth-2-yl)ethanone 4j displayed good inhibitory profile against Escherichia coli and Staphylococcus aureus which was about 50% and 25% of the Ampicillin (standard drug), respectively. The compounds, 4a and 4f showed relatively moderate inhibition against Psuedomonas aeruginosa and E. coli. In DNA photocleavage study, compounds 4c and 4d were found to be highly active and completely degraded both forms of DNA (SC and OC), even at a very low concentration of 1 μg (4c) under irradiation of UV light. However, 4h and 4f resulted in complete DNA degradation at 30 μg concentration. Moreover, 4h showed fluorescence at 15 μg concentration and increased the intensity of both bands of DNA (SC and OC) as compared to control. On the other hand, to valorize the biological potential, the compounds were screened for their cytotoxic activity on colon (HCT116 and HT29), prostate (DU145), ovarian (SKOV3) and lung (A549) cancer cell lines. The compound 4j was found to be cytotoxic to all the cancer cell lines, except SKOV3, with more selectivity towards the colon cancer cell lines (HCT116, HT29) and A549 lung cancer cell line. On A549 lung cancer cell line, 4j and 4k exhibited similar potency as carboplatin in inhibiting cell viability.
Department of Chemistry, M. M. University, Mullana-Ambala 133207, India. Electronic address: vinodbatan@gmail.com.
Vinod
V
Kumar
Department of Chemistry, M. M. University, Mullana-Ambala 133207, India.
Kamalneet
K
Kaur
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.
Deepkamal N
DN
Karelia
Department of Biotechnology, M. M. University, Mullana-Ambala 133207, India.
Vikas
V
Beniwal
Department of Pharmaceutical Chemistry, M. M. University, Mullana-Ambala 133207, India.
Girish Kumar
GK
Gupta
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.
Arun K
AK
Sharma
Department of Chemistry, M. M. University, Mullana-Ambala 133207, India.
Akhilesh Kumar
AK
Gupta
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000528:radiation effects; D053837:DNA Cleavage / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D055668:Photochemical Processes; D010957:Plasmids / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004247:DNA
Antibacterial; Anticancer; DNA photocleavage; Solvent free conditions