Synthesis and Analgesic Activity of New Analogues of Tyr-MIF Including Pyrrole Moiety

Abstract

Pain is one of many medical problems of modern society. Together with a number of other diseases such as heart attacks, strokes, tumors, etc. it ranks among the first in manifestation. There are a huge number of medical drugs more or less effective against pain in a practice. Globally, the searching of new molecules with analgesic activity and better selectivity or greater effect at lower doses continues. In addition, some groups trying to improve the properties of known molecules in medical practice as various heterocyclic compounds by modifying one or another of their part. Other groups work on the creation of new mimetics of natural molecules with well established physiological activity. In this global context, here we report the synthesis of two new compounds which are hybrid molecules between the specifically substituted pyrrole (Pyr) and analogues of Tyr-MIF-1 peptide. All investigations on the analgesic activity show better activity at the same dose than natural Tyr-MIF-1 peptide for the analogue Pyr-Tyr-Phe-Leu-Ala-OH. Compound Pyr-AlaLeu-Phe-Tyr-OH has no better effect comparable to that of the parent peptide. The obtained results clearly show that it is essential that Tyr residue occupies N-terminal position of MIF-1 analogue. The lack of better activity of the analogue Pyr-Ala-Leu-Phe-Tyr-OH reveals that Pyr residue does not influence on the analgesic activity. In addition we found that C-terminal amide function generally presented in natural MIF-1 is not absolutely necessary for activity.

Synthesis, In Silico Logp Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL

“…Sensory-discriminative, affective-emotional, and cognitive-evaluative components “build up” the mechanism of pain perception, resulting from dynamic interactions of multiple central and peripheral neural processes [ 6 , 7 ]. Although acute pain protects us from predictable harm, recurrent acute episodes and, especially, chronic pain deteriorate the quality of life, leading to discomfort and disability [ 8 ].…”

“…Although many substances, such as non-steroidal anti-inflammatory drugs, cyclooxygenase inhibitors, opioids, corticosteroids, etc. [ 8 , 24 , 25 ], are known to possess analgesic properties, their use is hampered by side effects, such as respiratory depression, nausea, clouding of consciousness, constipation, addiction, and tolerance [ 26 ]. Thus, the development of opioid drugs free of such effects is a major goal in “pain killer” research.…”

Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety

“…Thus, society is in a great need of new analgesics to limit the consequences of this public health issue and to overcome the undesired side effects of those medicaments currently used in the practice. Briefly, regardless of the source, pain is an uncomfortable feeling that often leads to discomfort and functional limitations [19]. Thus, conjugation of some known chemical compounds with a well-proven analgesic effect into hybrid structures with active peptide moiety seems to be an alternative for the creation of new molecules with better directionality and synergic effect as promising opioid agents.…”

Fused Pyrroles in Cholestane and Norcholestane Side Chains: Acaricidal and Plant Growth-Promoting Effects

“…The Paal–Knorr reaction [ 8 , 9 , 10 ], in which 1,4-dicarbonyl systems are converted into pyrroles by an acid-mediated dehydration cyclization in the presence of a primary amine, is a frequently used method for making pyrroles. The 1,4-dicarbonyl framework supplies the pyrrole’s four carbons, and the amine provides the nitrogen.…”