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

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 μM 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

Inhibitory effects of benzimidazole containing new phenolic Mannich bases on human carbonic anhydrase isoforms hCA I and II

New phenolic mono and bis Mannich bases incorporating benzimidazole, such as 2-(aminomethyl)-4-(1H-benzimidazol-2-yl)phenol and 2,6-bis(aminomethyl)-4-(1H-benzimidazol-2-yl)phenol were synthesized starting from 4-(1H-benzimidazol-2-yl)phenol. Amines used for the synthesis included dimethylamine, pyrrolidine, piperidine, N-methylpiperazine and morpholine. The CA inhibitory properties of these compounds were tested on the human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I and hCA II. These new compounds, as many phenols show moderate CA inhibitory properties

Synthesis and carbonic anhydrase inhibitory activities of new thienyl-substituted pyrazoline benzenesulfonamides.

A series of new thienyl-substituted pyrazoline benzenesulfonamides were synthesized and their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activities were tested on the human (h) isoforms hCA I and hCA II. The inhibition constant (Ki) of these sulfonamides were in the range of 232.16-637.70 nM toward the slow cytosolic isozyme hCA I, and in the range of 342.07-455.80 nM toward hCA II. Many of these compounds showed comparable inhibition with the reference sulfonamide acetazolamide, a clinically used drug. As the sulfonamide CA inhibitors (CAIs) show many therapeutic uses, these derivatives represent interesting examples of a novel class of such derivatives

Carbonic anhydrase inhibition and cytotoxicity studies of Mannich base derivatives of thymol

Mannich bases of thymol were synthesized. The aminomethylation reaction was realised in the ortho position of the phenol for compounds 2 (dipropylamine), 3 (benzylamine), and 4 (dibenzylamine) while it was from para position for 1 (dimethylamine), 5 (piperidine), 6 (morpholine) and 7 (N-methylpiperazine). The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were asssessed against hCA I and hCA II. All compounds moderately inhibited hCA I and hCA II. The cytotoxicity of the compounds against four human oral squamous cell carcinoma cell lines were compared those against three normal oral cells. Tumor specificity values were about 2 or slightly more for the compounds 2, 3, 4, 5 and 6. Compound 2 showed cytostatic activity against OSCC cell lines at 16 to 32-fold lower concentrations as compared with normal cells. This suggests that compound 2 can be considered as cytotoxicity enhancing drug candidate for further investigations

N-[2-(4-Bromo­benzo­yl)eth­yl]isopropyl­aminium chloride

The crystal structure of the title compound, C12H17BrNO+·Cl−, is stabilized by N—H⋯Cl and C—H⋯O hydrogen bonds, forming a three-dimensional network. The inter­actions framework is completed by C—H⋯π contacts between a methyl­ene group and the benzene ring of a symmetry-related mol­ecule

Synthesis and bioactivity studies of 1-aryl-3-(2-hydroxyethylthio)-1-propanones

A series of Mannich bases having piperidine moiety were reacted with 2-mercaptoethanol, leading to 1-aryl-3-piperidine-4-yl-1-propanone hydrochlorides. The cytotoxicity and carbonic anhydrase inhibitory activities of these new compounds were evaluated. Among the compounds, only one derivative, nitro substituent bearing EU9, showed an effective cytotoxicity, although weak tumor specificity against human oral malignant versus nonmalignant cells. The compound induced apoptosis in HSC-2 oral squamous cell carcinoma cells, but not in human gingival fibroblast. Chemical modifications of this lead are thus necessary to further investigate it as a drug candidate and to obtain compounds with a better activity profile

Carbonic anhydrase inhibitors. Phenols incorporating 2- or 3-pyridyl-ethenylcarbonyl and tertiary amine moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase

A series of phenols incorporating tertiary amine and trans-pyridylethenyl-carbonyl moieties were assayed as inhibitors of the beta-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA. One of these compounds was a low nanomolar ScCA inhibitor, whereas the remaining ones inhibited the enzyme with K(I)s in the range of 23.5-95.4 nM. The off-target human (h) isoforms hCA I and hCA II were much less inhibited by these phenols, with K(I)s in the range of 0.78-23.5 mu M (hCA I) and 10.8-52.4 mu M (hCA II). The model organism S. cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged

3-(4-Chloro­benzo­yl)-4-(4-chloro­phen­yl)-1-phenethyl­piperidin-4-ol

In the title compound, C26H25Cl2NO2, the piperidine ring adopts a chair conformation with a cis configuration of the carbonyl and hy­droxy substituents. The dihedral angle between the aromatic rings of the chloro­benzene groups is 24.3 (2)°. The phenyl ring forms dihedral angles of 59.4 (3) and 44.1 (3)° with the benzene rings. In the crystal, mol­ecules are linked by inter­molecular O—H⋯N and C—H⋯O hydrogen bonds and C—H⋯π inter­actions into layers parallel to the bc plane

Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents

1-Aryl-3-phenethylamino-1-propanone hydrochlorides 1-10, which are potentialpotent cytotoxic agents, were synthesized via Mannich reactions using paraformaldehyde,phenethylamine hydrochloride as the amine component and acetophenone, 4’-methyl-, 4’-methoxy-, 4’-chloro-, 4’-fluoro-, 4’-bromo-, 2’,4’-dichloro-, 4’-nitro-, 4’-hydroxyacetophenone or 2-acetylthiophene as the ketone component. Yields were in the87-98 % range. Of the compounds synthesized, compounds 2, 6-8 and 10 were new. Theoptimum reaction conditions were investigated by changing the mol ratios of the reactants,the solvents and the acidity levels using 1 and 10 as representative targets. It was observedthat the best mol ratio of the ketone, paraformaldehyde and phenethylamine hydrochloridewas 1:1.2:1 (compared with a 2:2.1 ratio), and the most suitable reaction medium wasethanol containing concentrated hydrochloric acid (compared with only ethanol or nosolvent). This study may serve as a guide for the conditions of the reactions to synthesizecompounds having similar chemical structures