José Quincoces Suarez

New antitumoral agents I: In vitro anticancer activity and in vivo acute toxicity of synthetic 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one and derivatives

This paper describes a new method for the preparation of 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one 1 and its derivatives 2-5. This set of synthetic compounds exhibited high antitumoral activities regarding in vitro screening against several human tumor cell lines as lung carcinoma NCI-460, melanoma UACC-62, breast MCF-7, colon HT-29, renal 786-O, ovarian OVCAR-03 and ovarian expressing the resistance phenotype for adriamycin NCI-ADR/RES, prostate PC-3, and leukemia K-562. Compounds were also tested against murine tumor cell line B16F10 melanoma and lymphocytic leukemia L1210 as well as to their effect toward normal macrophages. Specific activity against colon cancer cells HT-29 was observed for all tested compounds and suggests further studies with models of colon cancer. Compounds 1, 2, and 4 showed significant cytotoxic activity with IC(50) values 2.3 microM for all human cancer cell lines. Intraperitoneal acute administration of compound 1 and 2 showed very low toxicity rate.

Evaluation of anti-inflammatory effect of synthetic 1,5-bis(4-acetoxy-3-methoxyphenyl)-1,4-pentadien-3-one, HB2

This work describes the synthesis and anti-inflammatory properties of a pentadienone derivative, HB2. The treatment with HB2 produced anti-oedematogenic, anti-inflammatory and antinociception without change locomotors performance. Finally, HB2 reduced the nitric oxide and prostaglandin E(2) production on RAW 264.7 cells stimulated with LPS without changing the cell viability. Taken together, our results show, for the first time, that HB2 can modulate the inflammatory response when administered to mice.

Synthesis of Novel Anellated Pyranosides as Precursors of C‐Nucleoside Analogues Using Isopropyl 6‐O‐Acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose

Abstract Isopropyl 6‐O‐acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose (3) was converted to the corresponding 3‐[bis(methylthio)methylene] derivative 4 with a push–pull activated C–C double bond. Treatment of 4 with hydrazine and methylhydrazine afforded the pyrano[3,4‐c]pyrazol‐5‐ylmethyl acetates 5a and 5b, respectively. Desulfurization of compound 4 with sodium boron hydride yielded the 3‐[(methylthio)methylene]hexopyranosid‐2‐ulose 7. Compound 7 was reacted with amines to furnish 3‐aminomethylene‐hexopyranosid‐2‐uloses 8, 9. Reaction of 7 with hydrazine hydrate, hydrazines, hydroxylamine, and benzamidine afforded the pyrazolo, isoxazalo, and pyrimido anellated pyranosides (10–13). #Dedicated to Professor Dr. Günther Oehme on the occasion of his 65th birthday.

Synthesis and Reactions of Branched‐chain Anhydrouloses with Push Pull Functionality

The α-oxoketene dithioacetal 1 was demethylthiolated with sodium borohydride to give the branched chain anhydroulose 2 which yielded with amines the corresponding aminomethylene enuloses 3, 4 and 5. The heterocyclic anellated pyranose derivatives 6, 7 and 8 were prepared by reaction of 2 with hydrazine hydrate, methylhydrazine and hydroxylamine, respectively. By treatment of methylthiomethylene enulose 18 with guanidine, acetamidine and benzamidine the pyrimidoanellated pyranose derivatives 12—14 have been obtained.

Synthesis of C-nucleoside analogues starting from 1-(methyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-α-D-altropyranosid-2-yl)-4-phenyl-but-3-yn- 2-one

Abstract 1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one (4) was synthesized by the reaction of (methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)ethanal (2) with lithium phenylethynide and following oxidation. Compound 4 and hydrazine hydrate provided the 3(5)‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl‐methyl)‐5(3)‐phenyl‐1H‐pyrazole (5). The reactions of 4 with amidinium salts and a S‐methyl‐isothiouronium salt, respectively, furnished the pyrimidine C‐nucleoside analogues 6a–6c. Treatment of 4 with 2‐aminobenzimidazole afforded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐ylmethyl)‐4‐phenyl‐benzo [4,5]imidazo[1,2‐a]pyrimidine (7a). Compound 4 and sodium azide yielded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐1‐[5(4)‐phenyl‐1H(2H)‐1,2,3‐triazole‐4(5)‐yl]ethanone (8). #Dedicated to Professor Dr. Willi Kantlehner on the occasion of his 60th birthday.