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

Abstract

Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25-43%) and hCA II (6-25%) isoforms at 10 mM concentration of inhibitor, the compounds were more selective (1.5-5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.

Synthesis, molecular modeling, and biological evaluation of 4‐[5‐aryl‐3‐(thiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes

“…First, chalcones were synthesized via Claisen–Schmidt reaction as described in literatures . 2‐Acetylthiophene (2 g, 16 mmol) and the appropriate aromatic aldehyde (1.7 g for 1 , 2.0 g for 2 , 2.2 g for 3 , 2.0 g for 4 , 2.2 g for 5 , 3.0 g for 6 , 2.8 g for 7 , 1.8 g for 8 , 2.6 g for 9 , 2.6 g for 10, 16 mmol) were dissolved in ethanol (10 ml), and an aqueous solution of potassium hydroxide (10 ml, 40% w/v) was added dropwise into the reaction flask.…”

Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and cancer stem cells: Three for the price of one

“…There are also many other studies in which phenols and phenolic acids were investigated as CA IX inhibitors, but again, no CA IX‐selective inhibitors have been detected, and these data will be not discussed in detail here.…”

“…207 These aspects make the carboxylic acids the most versatile class of CAIs targeting CA IX, [206][207][208][209][213][214][215][216][217] but no specific CA IX-selective carboxylates were reported so far (there are on the other hand CA XII-selective inhibitors belonging to this chemotype). 217 There are also many other studies in which phenols and phenolic acids were investigated as CA IX inhibitors, 210,[218][219][220][221][222][223][224][225][226][227][228] but again, no CA IX-selective inhibitors have been detected, and these data will be not discussed in detail here.…”

New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6‐(3‐Halogenated phenyl‐2‐propen‐1‐oyl)‐2(3H)‐benzoxazolones

“…[ 27 ] The α,β‐unsaturated carbonyl system is responsible for the biological activities of the chalcones. [ 26,28 ] Various chalcone derivatives have been reported with many biological activities such as anti‐inflammatory, [ 29,30 ] antimicrobial, [ 31 ] antifungal, [ 32 ] antioxidant, [ 33 ] antimalarial, [ 34 ] antileishmanial, [ 35,36 ] anticancer, [ 37–39 ] cytotoxic, [ 40–42 ] CA inhibiting, [ 43–45 ] and anti‐invasive [ 46 ] activities.…”