Yaseen A. Al-Soud

Synthesis and properties of new substituted 1,2,4-triazoles: Potential antitumor agents

Cycloaddition of the reactive intermediates 4 with 1-(cyanomethyl)benzotriazole (5) and its N-2 isomer 9 furnished, after spontaneous rearrangements, the 1,2,4-triazole derivatives 8 and 10. Analogously, reaction of 4 with ethyl cyanoacetate lead to the 1,3,5-trisubstituted 1,2,4-triazoles 12, which gave on treatment with hydrazine the corresponding hydrazides 13. Treatment of 13d with galactose or phenyl isothiocayanate gave the 1-D-galactose-acylhydrazone 14 and the 1,2,4-triazole derivative 15, respectively. Compounds 8c; 10b,c; 13a,c and 14 were selected for the antitumor screening, whereby 8c, 13a, and 13c showed remarkable activity against leukemia, ovarian, renal and lung cancers (8c with Gl(50) of 0.70 microM, 0.07 microM against leukemia (CCRF-CEM and RPMI-8226), 0.02 microM against ovarian (OVCAR-3) and 0.60 microM against renal (CARKI-1) and lung cancers, respectively).

1,2,4-Triazoles: Synthetic approaches and pharmacological importance. (Review)

The synthetic routes of 1,2,4-triazole compounds as well as their pharmacological properties have been described. The review focuses intensively on two methods: cycloaddition reaction in the syntheses of various 1,5-dialky-1H-1,2,4-triazole derivatives from the reactive cumulenes with the nitrile precursors as well as the microwave irradiation method.

Novel fluorescent pH sensor based on coumarin with piperazine and imidazole substituents.

A new coumarin derivative containing piperazine and imidazole moieties is reported as a fluorophore for hydrogen ions sensing. The fluorescence enhancement of the studied sensor with an increase in hydrogen ions concentration is based on the hindering of photoinduced electron transfer from the piperazinyl amine and the imidazolyl amine to the coumarin fluorophore by protonation. The presented sensor has a novel design of fluorophore-spacer-receptor(1)-receptor(2) format, which is proposed to sense two ranges of pH (from 2.5 to 5.5) and (from 10 to 12) instead of sensing one pH range. A model compound, in which the piperazinyl ring is absent, was synthesized as well to confirm the novel pH sensing of the proposed sensor.

Synthesis of 1′-β-d-glucopyranosyl-1,2,3-triazole-4,5-dimethanol-4,5-bis(isopropylcarbamate) as potential antineoplastic agent

Abstract The title compound 5 was prepared from the 1-β- d -azido-glucose 1 via four steps. Alternatively, 5 was synthesized from 1 , via acetalation, cycloaddition with acetylene derivative, reduction, then carbamoylation followed by an acid hydrolysis.

In-Vitro Anti-HIV and Antitumor Activity of New 3,6-Disubstituted [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles and Thiadiazine Analogues

A series of [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles (7–15) and the thiadiazine analogues 16–18 have been synthesized under microwave irradiation (MWI). All synthesized compounds are evaluated for their antiviral activity against the replication of HIV‐1 and HIV‐2 activity in MT‐4. However, compounds 12 and 18 showed EC50 = 2.11 and 1.97 μg/mL. The results suggest that these compounds can be considered as a new lead in the development of antiviral agents. Compounds 4–18 were tested in vitro against a panel of tumor cell lines. All compounds are inactive against all the tumor sub‐lines, except 10 which exhibited activity against CD4+ human acute T‐lymphoblastic leukaemia of CC50 = 64 μM.

Synthesis and antiviral activity of 1-[1,5-dialkyl-1H-1,2,4-triazol-3-yl)methyl]thymines.

Cycloaddition of the intermediates 2 with 1‐(cyanomethyl)‐thymine 3 furnished the 1,2,4‐triazolium salts 4, which rearranged spontaneously to the protonated salts 5. Hydrolysis of 5, in situ, afforded the title compounds 6. Compounds 6a‐c were screened against HIV‐1 (IIIB), HIV‐2 (ROD), and human cytomegalovirus (HMCV) and showed poor or no activity, respectively.

Synthesis and reactions of 1,5- and 1,3-dialkyl-(d-manno-pentitol-1-yl)-1H-1,2,4-triazole nucleosides derived from 1-(chloroalkyl)-1-aza-2-azoniaallene salts

Abstract 1-(Chloroalkyl)1-aza-2-azoniaallene salts underwent cycloaddition with penta- O -benzoyl- d -mannonic acid nitrile to give several intermediates. The salts of these rearranged spontaneously to the protonated 1,2,4-triazoles, which hydrolysed, in situ, to the acyclic 1,2,4-triazole C-nucleosides. Deblocking of the latter afforded the free nucleosides. Analogous treatment of 1,1- tert -butylmethyl derivatives of 1-aza-2-azoniaaallene salts with penta- O -benzoyl- d -mannonic acid nitrile gave, after rearrangment and hydrolysis, acyclic C-nucleosides which on deblocking furnished the free nucleosides. Acetalation of 1-ethyl-3-( d - manno -pentitol-1-yl)-5-methyl-1 H -1,2,4-triazole and 5-( d - manno -pentitol-1-yl)-3-methyl-1-(1,2,4-trichlorophenyl)-1 H -1,2,4-triazole with acetone and dimethoxypropane in the presence of acid afforded their 2,3:4,5-diacetal derivatives

NEW GLYCOSYL-(CARBOXAMIDE)-1,2,3-TRIAZOLE-N-NUCLEOSIDES: SYNTHESIS AND ANTITUMOR ACTIVITY

ABSTRACT A series of potential bioactive compounds, 1-glucopyranosyl-1,2,3-triazole-4,5-dimethylcarboxylate, 1-glucopyranosyl-1,2,3-triazole-4,5-N-dicarboxamide,-dialkyl-dicarboxamide-N-nucleosides and 6-amino-4H-1-(β-D-glucopyranosyl)-8-hydroxy-1,2,3-triazolo[4,5-e][1,3]-diazepin-4-one, were synthesized. Primary activity screening of the novel nucleosides showed poor or no anticancer activity against breast, lung and CNS tumors.

Synthesis, Characterization and anti-HIV and Antitumor Activities of New Coumarin Derivatives

A new series of coumarin and benzofuran derivatives were synthesized as potential non-nucleoside reverse transcriptase inhibitors (NNRTIs) by reacting, separately, 4-bromomethylcoumarins, their sulphonyl chlorides, and ethyl 3-(bromomethyl)-6-methoxy-1-benzofuran-2-carboxylate with different imidazoles and their benzo analogs. The antiviral (HIV-1, HIV-2) properties of the newly synthesized compounds were investigated in vitro and all compounds were found to be inactive, except 10 which showed inhibition of HIV-2 with EC50 > 0.51 μgmL−1. The in vitro cytotoxicity of 17 and 19 was assayed against a panel of tumor cell lines consisting of CD4 human T-cells.

New sulphonamide and carboxamide derivatives of acyclic C-nucleosides of triazolo-thiadiazole and the thiadiazine analogues. Synthesis, anti-HIV, and antitumor activities. Part 2.

A new series of acyclic C-nucleosides 1′,2′-O-isopropylidene-D-ribo-tetritol-1-yl)[1,2,4] triazolo[3,4-b][1,3,4]thiadiazoles bearing arylsulfonamide (5–8) and arylcarboxamide (9–12) residues have been synthesized under microwave irradiation. Thiadiazines 13–15 have been analogously prepared, and upon acid hydrolysis, afforded the free nucleosides 16–18. The new synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compound 7 was also screened against a panel of tumor cell lines consisting of CD4 human T-cells.