Synthesis and Antitumor Activity of 3‐(2‐Phenyl‐1,3‐thiazol‐4‐yl)‐1H‐indoles and 3‐(2‐Phenyl‐1,3‐thiazol‐4‐yl)‐1H‐7‐azaindoles

Abstract

Given the potent antimicrobial, antiviral, and antitumor activities of many natural products, there is an increasing interest in the synthesis of new molecules based on natural compound scaffolds. Based on a 2,4-bis(3'-indolyl)imidazole skeleton, two new series of phenylthiazolylindoles and phenylthiazolyl-7-azaindoles were obtained by Hantzsch reaction between substituted phenylthioamides and the α-bromoacetyl derivatives. Some azaindole derivatives, tested at the National Cancer Institute against a panel of ∼60 tumor cell lines derived from nine human cancer cell types, showed inhibitory effects against all cell lines investigated at micromolar to nanomolar concentrations. Two of them exhibited a high affinity for CDK1, with IC(50) values of 0.41 and 0.85 μM. These promising results will set the foundation for future investigations into the development of anticancer therapies.

Synthesis and Antitumor Activity of New Thiazole Nortopsentin Analogs

“…N- SO 2 Ph protected indoles 10a – c [31,32] and 1-(1 H -indol-3-yl)ethanone 7c (90%) were synthesized from the commercially available indoles 8a – c or 1-(1 H -indol-3-yl)ethanone 7a by reaction with benzenesulphonyl chloride and sodium hydride (NaH), in tetrahydrofuran (THF); whereas methylated compounds 9a – c and 7b were prepared as previously reported [26,30]. …”

“…Other structural manipulation of the natural product also involved one or both indole units producing 3-[(2-indolyl)-5-phenyl]pyridine and 3-(2-phenyl-1,3-thiazol-4-yl)-1 H -7-azaindole derivatives, which showed significant antiproliferative activity and inhibited CDK1 (Chart 2) [25,26]. …”

“…Considering the interesting biological activity of nortopsentin analogs and in particular of 3-(2-phenyl-1,3-thiazol-4-yl)-1 H -7-azaindole derivatives previously reported by us [26], herein we report the synthesis of new derivatives of type 4 , 5 (Scheme 1) and 6 (Scheme 2), in which one of the two indole units was replaced by a naphthyl portion, to further investigate the contribution of the aryl moiety on biological activity. The antiproliferative activity of the novel compounds was evaluated in different human cancer cell lines and further studies were performed on the most active derivatives, in order to clarify their mechanism of action.…”

Synthesis of substituted isoindolo[2,1-a]quinoxalin-6-yl–amino and 6-imino-5-yl thiourea derivatives

“…Quinoxalinylethylpyridylthioureas (QXPTs) of type 1 and 2 ( Figure 2) represent another class of NNRTIs; many compounds showed a potent activity against both HIV-1 wild-type RT and various HIV-1 mutants HIV-1 RT. 16 Considering the good experience reached in the course of our researches on polycyclic nitrogen systems, bearing pyrrole, [17][18][19][20][21][22][23][24] indole, [25][26][27][28][29][30][31][32][33][34][35] isoindole 36-38 and indazole …”

Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

“…These metabolites have been widely reported, as well as many synthetic analogs with interesting antitumor activity [5,6,7,8,9,10]. The marine sponge, Theonella sp.…”