N-Hydroxy-N′-aminoguanidines as anti-cancer lead molecule: QSAR, synthesis and biological evaluation

Titanium-Catalyzed Hydrohydrazination of Carbodiimides

“…Aminoguanidines ( I ) exhibit interesting physiological behavior as dopamine β-oxidase inhibitors and antihypertensives . Moreover, anti-HIV activity has been found for N -glycosyl- N ′-(4-arylthiazolyl)aminoguanidines ( II ) and several N -hydroxy- N ′-aminoguanidines ( III ) display antitumor activity . Whereas the underlying mechanisms for this activity remain to be established, they may well be related to their properties as radical scavengers and antioxidants, as studied recently by Tong et al Further development of their chemistry requires efficient preparative protocols for N -aminoguanidines.…”

Synthesis and Anticancer Activities of Novel Guanylhydrazone and Aminoguanidine Tetrahydropyran Derivatives

“…The oxidation of tetrahydropyran alcohols to the corresponding ketones 8a-c (step iii, Scheme 1) was performed in high yields by using PCC in dichloromethane as a solvent (95%-98% yields). The guanylhydrazone 2-4 ( Figure 1) were prepared in quantitative yields (100% yields) by reacting ketones 8a-c with aminoguanidine hydrochloride and ethanol as a solvent (no catalysts were used) promoted by 5 min of microwave In connection to our interest in the stereoselective synthesis of tetraydropyran derivatives using the Prins cyclization reaction [14][15][16][17][18], and considering that guanylhydrazone [19] and aminoguanidine groups [20,21] potentiate the anticancer activity of some drugs, and these nitrogenated bases could be considered pharmacophoric points, we present in this article the syntheses of six novel tetrahydropyranyl guanylhydrazone and aminoguanidine 2-7 ( Figure 2). That way, we performed in vitro evaluation for anticancer activity against cancer cell lines, such as the chronic myeloid leukemia (K562), human acute myeloid leukemia (HL-60), human breast adenocarcinoma (MCF-7), human colon adenocarcinoma (HT-29), and L929 (murine fibroblast) and the human peripheral blood of patients with chronic myeloid leukemia (PBMC/CML) cells.…”

“…Our experimental work starts with the preparation in good yield of homoallylic alcohols shown in Scheme 1 (step i) from the Barbier reaction [21] between the corresponding aldehydes (benzaldehyde, 4-fluorobenzaldehyde and 2-naphthaldehyde) with allyl bromide in the presence of stannous chloride (96%-98% yields). In step ii the corresponding tetrahydropyran rings of 1a-c are prepared with control of relative configuration (2,4,6-cis) from the Prins cyclization reaction [12], followed by hydrolysis of the acetyl intermediate with potassium carbonate in methanol (60%-63% yields).…”

QSAR Studies on Hydroxamic Acids: A Fascinating Family of Chemicals with a Wide Spectrum of Activities

“…They have been found to inhibit DNA synthesis by inhibiting specifically the R2 subunit of the enzyme ribonucleotide reductase, which is one of the most widely accepted targets for the development of anticancer agents. , Hydroxamic acids contain pharmacophoric features similar to those of many other anticancer agents, such as hydroxyaminoguanidines (HAGs), − hydroxysemicarbazide­(HSs), and amidoximes, which have been widely studied for their anticancer activity. The common pharmacophoric feature in all of them is {−C­(X)­NHOH, X = O, NH}, which has been identified as the basic pharmacophore for anticancer activity. − For all of these groups of compounds, a common four-point pharmocophore was developed by Basu et al that consisted of two H-bond acceptors (A 1 , A 2 ), one H-bond donor (D), and one aromatic ring (R), in which an aminoguanidine ( 48 ) is shown to be embedded (Figure ). The interpharmacophoric distances for this model are shown in Figure a as well as in Table .…”

“…(a) Distances between the various pharmacophoric features, and (b) the most active molecule ( 48 ) shown to be embedded in the map. Reprinted with permission from ref . Copyright 2011 Elsevier.…”