Mannich bases in medicinal chemistry and drug design

Abstract

The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors.

Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases

“…Mechanisms of anticancer effects of chalcones appear to be complex and frequently multimodal and include cell cycle disruption, inhibition of angiogenesis, inhibition of tubulin polymerization, induction of apoptosis, inhibition of topoisomerase, and inhibition of kinases [13][14][15][16] . Mannich bases are generally formed by the reaction between a compound containing a reactive hydrogen atom, formaldehyde, and mostly secondary amine 2,17 . The chemistry of Mannich bases has been the subject of wide and increasing interest, due to their biological activities such as analgesic, antimalarial, anticonvulsant, antipsychotic, cytotoxic, antiinflammatory, and antimicrobial activities [3][4][5]8,9,[17][18][19][20][21][22] .…”

“…Mannich bases are generally formed by the reaction between a compound containing a reactive hydrogen atom, formaldehyde, and mostly secondary amine 2,17 . The chemistry of Mannich bases has been the subject of wide and increasing interest, due to their biological activities such as analgesic, antimalarial, anticonvulsant, antipsychotic, cytotoxic, antiinflammatory, and antimicrobial activities [3][4][5]8,9,[17][18][19][20][21][22] . In addition, the Mannich bases of several bioactive molecules such as Taxol (anticancer agent), SCH48461 (anticholesterol agent), Tramadol (analgesic), Osnervan (antiparkinson), and Moban (neuroleptic) were prepared and they showed increased bioactivities comparing to the parent compounds 23 .…”

“…The introduction of aminoalkyl Mannich side chain into Topotecan increased the water solubility of this anticancer agent 23 . Conversion of phenolic chalcones into their corresponding Mannich bases is often accompanied by increased bioactivity in in vitro and/or in vivo studies 2,9,14,17,22,24 . This situtation has been attributed to the deamination skill of a Mannich base to generate additional alkylation site to chalcones for additional nucleophilic attack by cellular thiols such as glutathione or cysteine to lead dramatic inrease by Mannich bases according to sequential cytotoxicity 2,15 .…”

Discovery of Novel Isatin-Based p53 Inducers

“…The identified compounds represent a combination of Mannich 29 and Schiff bases that are known to have a tendency for hydrolysis. Therefore, we separately analyzed two different possible hydrolysis reactions ( Figure S7) of IMSBD4 using UV−vis spectrometry.…”

Design, Synthesis, and in vitro Antimycobacterial Activity of Propylene‐tethered Isatin Dimmers

“…Numerous isatin derivatives have been screened for their anti-TB activities, such as isatin Mannich bases [11][12][13], aminopyrimidinimino-isatin hybrids [14][15][16][17], thiosemicarbazone-isatin hybrids [18][19][20], methylene tethered fluoroquinolone-isatin hybrids [21][22][23], ethylene linked fluoroquinolone-isatin hybrids [24][25][26][27], and 1,2,3-triazole tethered fluoroquinolone-isatin hybrids [28][29][30], and some of them exhibited excellent in vitro and in vivo activities against both drug-susceptible and drug-resistant strains of MTB. Compared with the corresponding monomeric derivatives, the dimmeric compounds often display some unique properties such as enhanced catalytic capacity [31,32] and antimalarial activity [33], and some isatin dimmers showed potential antitumor activities [34,35], so it is reasonable to design isatin dimmers that may be an incensement of their anti-TB activities.…”