Related Mannich Bases Research Articles

ChemInform Abstract: Synthesis of Some New S‐Alkylated 1,2,4‐Triazoles, Their Mannich Bases and Their Biological Activities.

AbstractA variety of new S‐alkylated triazoles (IX) (19 examples) and related Mannich bases (XII) are synthesized and evaluated for their pharmacological activities.

Synthesis and Anti-Inflammatory Activity of Chalcones and Related Mannich Bases

Chalcones and Mannich bases have been reported to present antiinflammatory activities as well as inhibitory activities on several factors implicated in inflammation disorders. A series of chalcones and some related Mannich bases were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde. Mannich bases were derived from chalcones, with formaldehyde and the corresponding amine. The compounds were tested in vitro for their ability to inhibit various enzymes involved in the arachidonic acid cascade, for their antioxidant behaviour and in vivo for anti-inflammatory activity. Some chalcones and Mannich bases present strong anti-inflammatory and antioxidant activities. Almost all the tested compounds present high inhibitory activity on lipid peroxidation. Some compounds showed potent inhibitory effect on superoxide anion formation. Among the tested compounds 5 and 6 showed the highest lipoxygenase (LO) inhibitory activity. All the tested compounds inhibit both the proteolytic and esteratic activities of trypsin and chymotrypsin. The results indicated that the anti-inflammatory effects of the compounds were partially mediated, through their antioxidant activity. Attempts to correlate quantitatively structure with activity revealed that lipophilicity and molar refractivity influence the biological response.

The energy of the intramolecular hydrogen bond in chloro-substituted N-methyl-salicylidene imines

The energetic effects of the conformational rearrangement of eight Schiff bases, differently chloro-substituted, are discussed on the basis of the results of B3LYP/6-31+G(d,p) calculations. The proton transfer tautomers as well as “open”-non-hydrogen-bonded forms were considered. It was found, that the hydrogen-bonded forms have the lowest energy, but the second most stable were the proton transfer states with an O…H N intramolecular hydrogen bond. The proton transfer in Schiff bases dominates in comparison to other conformational rearrangements. This is important for the understanding of thermochromic and photochromic properties of these molecules. By using a thermodynamic cycle, the steric effects connected with chelate ring formation are estimated to be up to 5 kcal/mol, much higher than in related Mannich bases (∼1 kcal/mol) which do not form resonance assisted hydrogen bonds. Accounting these effects the “real” value of the energy of hydrogen bond formation was estimated to be 15 kcal/mol which increases with growing number of chlorine atoms up to 16.5 kcal/mol for 4,5,6-trichloro substitution.

Antimycobacterial arylidenecyclohexanones and related Mannich bases.

Several series of 2-arylidenecyclohexanones and related Mannich bases as well as various 2,6-bis(arylidene)cyclohexanones were evaluated against Mycobacterium tuberculosis H37Rv. Using a concentration of 12.5 microg/ml, nearly half of the unsaturated ketones inhibited the growth of the microorganism by 21-66% while all of the Mannich bases achieved 99% or greater inhibition. The relative hydrophobicities and widths of the molecules may have been contributing factors as to whether bioactivity was present or absent. Two of the Mannich bases demonstrated noteworthy potencies towards Mycobacterium avium. The conclusion was drawn that Mannich bases of 2-arylidenecyclohexanones represent a novel class of antimycobacterials.

Proton Transfer Equilibria in Schiff Bases with Steric Repulsion

The proton transfer equilibria in CH2Cl2 solutions of 2-(α-(N-methylimino)ethyl)phenol (1), 2-(α-(N-methylimino)ethyl)-4,6-dichlorophenol (2) and 2-(α-(N-propylimino)ethyl)-4,6-dichlorophenol (3) are studied by UV−vis, 1H NMR, and FT-IR spectra as a function of temperature. Thermodynamic parameters of the proton transfer reaction have been determined. It has been demonstrated that introducing of the methyl substituent into the CC(H)N moiety of the Schiff bases alters the tautomeric equilibrium in favor of the proton transfer forms in comparison with Schiff bases deprived of such substituent and related Mannich bases. Solvatochromy of electronic absorption in Schiff bases is evidence that the proton transfer state is neither zwitterionic nor orthoquinoid in their character but has to be taken as a resonance hybrid of these forms. According to this, a scheme of proton transfer equilibria specific for Schiff bases is proposed, which is in agreement with numerous structural evidences. The B3LYP/6-31G(d,p) frequency calculations performed for both the molecular and proton transfer forms precisely reproduce the experimental spectra measured as a function of temperature. The calculations show that the ν(CN) band assignment, widely discussed in the literature, is ambiguous because of the strong dependence of normal coordinates content on the character and conformation of particular forms of molecules. The calculations definitely show that the protonation of the CNR group decreases the force constants of the CN bonds, in spite of numerous opposite suggestions in the literature.

Preliminary approach to estimation and prediction of infrared spectroscopy for Mannich bases by atomic electronegativity distance vector (VAED)

Systematical studies were made on infrared spectroscopy (IR) and its regularity of vibration frequency. By applying a novel molecular structural descriptor vector containing four elements, called atomic electronegativity (EN) distance vector (VAED) expressed in the form of force, to characterize the chemical environment of various atoms in Mannich bases, the quantitative relationship models of IR of Mannich bases were established with respect to their VAED descriptors, based on multiple linear regression (MLR) analysis. In order to demonstrate the modeling stabilities and predictive abilities of diverse models, a cross validation (CV) with the leave-one-out (LOO) procedure was performed for each modeling equation. For the first panel of the 17 examined analogous Mannich bases, the correlation coefficient ( R) between the observed and estimated vibration frequencies and standard deviation (S.D.) both for the double covalent bonds, C, O ami PO are 0.9782, 0.9817, 9.1170 and 11.0649; and the corresponding R and S.D. obtained by the CV method are 0.9496, 0.8829, 14.1186 and 27.2829, respectively, which shows that the quantitative structure-spectrum relationship (QSSR) models are quite stable and have both good estimative results and fine predictive capabilities. For the second panel of the 16 examined Mannich bases, the results still seem satisfied since the QSSR model is stable and could roughly estimate and predict the vibration frequency of the CO bond for the other related Mannich bases.

Substituted acrylophenones and related mannich bases as possible spermicides and inhibitors of HIV envelope glycoprotein–CD4 interaction

Several appropriately substituted 4-(dialkylamino-alkyl)-substituted-styryl-alkyl ketones or acetophenones were prepared and subjected to the Mannich reaction to yield compounds that would incorporate both α,β-unsaturated keto groups and a substituted aminomethyl function with or without another olefinic moiety at position 4. The spermicidal activity of the prepared compounds was evaluated. Several compounds 2d, 4a and 4e were found to possess spermicidal activity at 0.005% concentration, while compounds 2a, 2c, 2f, 3a and 4b were active at 0.01% concentration. Compounds 2a, 2c, 3a, 4a and 4e also inhibited the interaction between recombinant HIV Env and CD4. Out of these, compound 2c was found to be most active.

Cytotoxic 2,6-bis(arylidene)cyclohexanones and related compounds

A number of 2-arylidenecyclohexanones 1, 2,6-bis(arylidene)cyclohexanones 2 and related Mannich bases 3– 5 were prepared. Various torsion angles as well as atomic charges on olefinic carbon atoms were determined by molecular modelling on all compounds. These molecules showed cytotoxicity towards murine P388 and L1210 cells as well as to human Molt 4/C8 and CEM T-lymphocytes. The average cytotoxicity of the dienones 2 was more than three times greater than was found with the monoarylidene analogues 1, and, in general, were slightly more cytotoxic than the Mannich bases 3– 5. A number of the compounds displayed potency towards a panel of human tumour cell lines and most of the representative compounds in series 2– 5 were selectively toxic to colon cancers and leukaemic cells.

Sequential cytotoxicity: a theory evaluated using novel 2-[4-(3-aryl-2-propenoyloxy)phenylmethylene]cyclohexanones and related compounds.

Five series of novel compounds were synthesized in order to evaluate the theory of sequential cytotoxicity which seeks to exploit the view that various cancer cells are particularly susceptible to successive attacks by cytotoxic agents. The compounds prepared were various 2-[4-(3-aryl-2-propenoyloxy)phenylmethylene]cyclohexanone s 1 and the related Mannich bases 2. In addition the analogues 3-5 lacking an olefinic bond in the ester group were also synthesized, which were predicted to be less cytotoxic than the compounds of series 1 and 2. The atomic charges at the potential sites for interaction with cellular constituents were determined by molecular modeling calculations. The biodata obtained from murine and human neoplastic cells revealed that the predictions made regarding the viability of the theory were fulfilled in approximately two-thirds of the cases indicating that further investigation of this hypothesis is warranted. In addition, the significant potencies of some of the Mannich bases toward human tumor cell lines, in particular coupled to their selective toxicity toward human leukemic and colon cancer cells, confirms their usefulness in serving as lead molecules for further development. A preliminary investigation into the mode of action of representative compounds revealed their ability to induce apoptosis and inhibit the biosyntheses of ribonucleic acid and proteins.

Anticancer and Cytotoxic Properties of Mannich Bases

This review outlines the chemistry and anticancer and cytotoxic properties of certain Mannich bases. It is divided into four parts. The first section summarizes briefly various investigations undertaken by other researchers of the chemical and pharmacological properties of a number of Mannich bases against neoplasms. The remaining portions of this review are summaries of work undertaken in this laboratory. The second part presents the following aspects of the anticancer properties of various Mannich bases namely differences in antileukemic activity between certain conjugated styryl ketones and the related Mannich bases, intramolecular cyclization of various acyclic Mannich bases and the effect on anticancer activity of such a process, prodrug approaches with a view to obtaining preferential toxicity to cancerous rather than normal cells and finally the effect on antineoplastic properties of introducing a second basic centre into these compounds. The third section summarizes the promising in vitro activities of different acyclic Mannich bases against the WiDr human colon cancer cells and the preparation of a group of Mannich bases which are effective against certain drug resistant malignant cells. The evidence for and evaluations of a theory proposed by one of the authors called sequential cytotoxicity is presented followed by a description of the very high cytotoxicity of some 4-piperidones; a group of compounds which may be regarded as cyclic Mannich bases. Finally, some biochemical properties of certain of these compounds are outlined especially with reference to their causing inhibition of respiration in mitochondria, particularly in those organelles obtained from neoplastic tissue.

The reaction of some nuclear substituted acyclic conjugated styryl ketones and related Mannich bases with ethanethiol

The second order rate constants for the reaction of ethanethiol with a number of conjugated nuclear-substituted styryl ketones and related Mannich bases in 50% aqueous acetonitrile was undertaken. Variation of the alkyl group adjacent to the carbonyl function was accompanied by altered avidity to ethanethiol which was explained as being due in part to the varying inductive effects of the alkyl groups which would, in turn, affect the stability of the reaction intermediates. The greatest disparity in reactivity between groups of compounds was between the ketones and analogous Mannich bases which was in accord with the marked difference in bioactivities between these two groups of compounds.

Evaluation of Nuclear‐substituted Styryl Ketones and Related Compounds for Antitumor and Cytotoxic Properties

A number of nuclear‐substituted styryl ketones, the related Mannich bases, and allyl alcohols were synthesized and evaluated for antitumor activity, principally in the L‐1210 lymphoid leukemia and P‐388 lymphocytic leukemia screening tests. The cytotoxicity of some of these compounds assessed in Eagle's 9KB carcinoma cell culture system was also recorded. Two of the Mannich bases showed promising levels of activity in the P‐388 screening; of the results obtained to date, over one‐third of the derivatives showed cytotoxicity at dose levels of 1–3 ppm. Other pharmacological results of these compounds are briefly reported.

Beta-amino ketones. Synthesis and some biological activities in mice of 3,3-dialkyl-1,2,3,4-tetrahydro-4-quinolinones and related Mannich bases.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT.beta.-Amino ketones. Synthesis and some biological activities in mice of 3,3-dialkyl-1,2,3,4-tetrahydro-4-quinolinones and related Mannich basesAspi B. Daruwala, James E. Gearien, William J. Dunn III, Phillipe S. Benoit, and Ludwig BauerCite this: J. Med. Chem. 1974, 17, 8, 819–824Publication Date (Print):August 1, 1974Publication History Published online1 May 2002Published inissue 1 August 1974https://doi.org/10.1021/jm00254a008RIGHTS & PERMISSIONSArticle Views312Altmetric-Citations20LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (714 KB) Get e-Alerts Get e-Alerts

Studies on Antibiotics and Related Substances. XVIII. The Synthesis of 5-Methyl-2-methylenecyclopentanone-3-carboxylic Acid, an Antitumor Substance, and Related Mannich Bases

Abstract 1) The Mannich reaction of 5-methylcyclopentanone-3-carboxylic acid with formaldehyde and dimethylamine hydrochloride gave a mixture of 2-(dimethylaminomethyl)-5-methylcyclopentanone-3-carboxylic acid (VI) and two kinds of geometrical isomers of 5-(dimethylaminomethyl)-5-methylcyclopentanone-3-carboxylic acid (IIa and IIb), from which IIa, an unstable methiodide (VII) of methyl ester of VI, and IIb were isolated. 2) Methyl 2-(dimethylaminomethyl)-5-methylcyclopentanone-3-carboxylate methiodide (VIII) was degraded to give methyl 5-methyl-2-methylencylopentanone-3-carboxylate (IX), which was then hydrolyzed to 5-methyl-2-methyleneclycopentanone-3-carboxylic acid (X), a homolog of sarkomycin. 3) The steric relation between IIa and IIb has been discussed. 4) The destructive distillation of methyl 2-(dimethylaminomethyl)-5-methylcyclopentan-one-3-carboxylate (VII), followed by hydrolysis, afforded 2,5-dimethylcyclopenten-1-one-3-carboxylic acid (XII), an isomer of X. It was found that the product was obtained also by the thermal decomposition of the methyl ester hydrochloride of IIa. This funding may be accounted for on the assumption that a rearrangement of the dimethylaminomethyl group occurred through a kind of retrograde Mannich reaction. 5) Some derivatives of the above-mentioned Mannich bases were described. 6) Both X and its methyl ester were found to possess antitumor and antibacterial activities.