Rationally Developed Organic Salts of Tolfenamic Acid and Its β-Alanine Derivatives for Dual Purposes as an Anti-Inflammatory Topical Gel and Anticancer Agent.
A new series of primary ammonium monocarboxylate (PAM) salts of a nonsteroidal anti-inflammatory drug (NSAID), namely, tolfenamic acid (TA), and its β-alanine derivatives were generated. Nearly 67 % of the salts in the series showed gelling abilities with various solvents, including water (biogenic solvent) and methyl salicylate (typically used for topical gel formulations). Gels were characterized by rheology, electron microscopy, and so forth. Structure-property correlations based on single-crystal and powder XRD data of several gelator and nongelator salts revealed intriguing insights. Studies (in vitro) on an aggressive human breast cancer cell line (MDA-MB-231) with the l-tyrosine methyl ester salt of TA (S7) revealed that the hydrogelator salt was more effective at killing cancer cells than the mother drug TA (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay); displayed better anti-inflammatory activity compared with that of TA (prostaglandin E2assay); could be internalized within the cancer cells, as revealed by fluorescence microscopy; and inhibited effectively migration of the cancer cells. Thus, the easily accessible ambidextrous gelator salt S7 can be used for two purposes: as an anti-inflammatory topical gel and as an anticancer agent.
Department of Organic Chemistry, Indian Association for the Cultivation of Science, 2A&2B Raja S.C. Mullick Road, Kolkata, 700032, West Bengal, India), Fax: (+91) 33-2473-2805.
Rumana
R
Parveen
Department of Organic Chemistry, Indian Association for the Cultivation of Science, 2A&2B Raja S.C. Mullick Road, Kolkata, 700032, West Bengal, India), Fax: (+91) 33-2473-2805.
Bommagani
B
Sravanthi
Department of Organic Chemistry, Indian Association for the Cultivation of Science, 2A&2B Raja S.C. Mullick Road, Kolkata, 700032, West Bengal, India), Fax: (+91) 33-2473-2805.
Parthasarathi
http://orcid.org/0000-0002-1011-2386
P
Dastidar
D000287:Administration, Topical; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D013050:Spectrometry, Fluorescence; D015091:beta-Alanine / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D062367:ortho-Aminobenzoates; D015091:beta-Alanine; C009500:tolfenamic acid
cancer; gels; inflammation; structure-activity relationships; supramolecular chemistry