Nuclear-substituted styryl ketone analogs: effects on neoplasms, microorganisms, and mitochondrial respiration of tumorous and normal cells.
Analogs of some antineoplastic and cytotoxic Mannich bases derived from conjugated styryl ketones were prepared and evaluated for activity in the P-388 lymphocytic leukemia screen. Most of the new compounds had lower antineoplastic and murine toxicity than the parent compounds. Antimicrobial evaluation of some oximes and alcohols related to the Mannich bases revealed activity against certain Gram-positive bacteria and fungi. Primary pharmacological evaluation showed that some compounds containing a dimethylaminomethyl group displayed analgesic and antihistaminic properties. Five of the Mannich bases were evaluated as respiratory inhibitors in mitochondria derived from hepatic tumors, liver tissue from tumor-bearing animals, and normal rat liver. No statistical difference between the sensitivity of the three tissues to the compounds was obtained.
D000588:Amines / Q000138:chemical synthesis*; D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D006633:Histamine Antagonists / Q000494:pharmacology; D007659:Ketones / Q000138:chemical synthesis*; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis*
D000588:Amines; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D006633:Histamine Antagonists; D007659:Ketones; D008352:Mannich Bases; D013343:Styrenes