Synthesis and anticancer activity evaluation of new 1,2,3-triazole-4-carboxamide derivatives

Pokhodylo, Nazariy T.; Shyyka, Olga Ya.; Matiychuk, V. S.

doi:10.1007/s00044-013-0841-8

Cited by 70 publications

(33 citation statements)

References 21 publications

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“…These compounds were synthesized and analyzed as described in sections 4.1.3. and 4.1.4. Compounds 2f , 25 3a , 26 3b , 27 3e , 15 3f , 25 3g , 28 3h , 28 3i , 29 3j , 29 3k , 18 3l , 18 4h , 30 15a , 20 and 15h 31 are commercially available and/or have been reported before. These compounds were synthesized and analyzed as described in sections 4.1.2. , 4.1.3. and 4.1.4. using partially different methods as described previously .…”

Section: Experimental Methodsmentioning

confidence: 99%

Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

Khalil

Edwards

Rappleye

et al. 2015

Bioorganic & Medicinal Chemistry

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Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 µM) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Edwards, JA et al. Antimicrob. Agents Chemother. 2013, 57:4349-5359). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC50s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic Structure-Activity-Relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain Selectivity Indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC50s of 0.4 µM. For these analogues, SIs of 92 - >100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity.

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Section: Experimental Methodsmentioning

confidence: 99%

Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

Khalil

Edwards

Rappleye

et al. 2015

Bioorganic & Medicinal Chemistry

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“…In mostc ases, 3-arylbenzisoxazoles are still prepared through organic reactions such as the intramolecular cyclization of 2-azidobenzophenones or the reactions of nitrobenzene derivatives with phenylacetonitrile derivatives (Scheme 1, middle and bottom). [7] However,f or these two methods, the substrate scope is limited because of the difThe Pd-catalyzed direct arylation of 2,1-benzisoxazole with aryl bromidest oa ccess 3-arylbenzoisoxazoles proceeds in moderate-to-high yields with 1mol %P d(OAc) 2 or 2mol % PdCl(C 3 H 5 )(dppb) (dppb = 1,4-bis(diphenylphosphino)butane) as the catalystsa nd KOAc as an inexpensive base. Aw ide variety of (hetero)aryl bromides have been employed successfully.…”

Section: Introductionmentioning

confidence: 99%

Reactivity of 2,1‐Benzisoxazole in Palladium‐Catalyzed Direct Arylation with Aryl Bromides

et al. 2016

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The Pd‐catalyzed direct arylation of 2,1‐benzisoxazole with aryl bromides to access 3‐arylbenzoisoxazoles proceeds in moderate‐to‐high yields with 1 mol % Pd(OAc)2 or 2 mol % PdCl(C3H5)(dppb) (dppb=1,4‐bis(diphenylphosphino)butane) as the catalysts and KOAc as an inexpensive base. A wide variety of (hetero)aryl bromides have been employed successfully. Moreover, arylations followed by benzisoxazole ring opening allowed the preparation of 2‐aminobenzophenones in only two steps.

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“…Furthermore, 1,2,3‐triazoles are able to form hydrogen bonds, they are not protonated at the physiological pH, and are also stable to oxidation and reduction as well as to many enzymatic reactions . Several compounds of the 1,2,3‐triazole family have exhibited a broad spectrum of biological activities, such as anti‐inflammatory , anticonvulsants , antiviral , anticancer , antimicrobial agents , as well as β‐lactamase inhibitors and dopamine D2 receptor ligands related to schizophrenia . Since 1997, when the first acyclic 1,2,3‐triazolenucleosides have been obtained by Lazrek et al , many efforts have been made by several research groups to synthesize more potent antiviral and anticancer nucleoside analogs having both natural and modified nucleobases (Fig.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3‐Triazole Nucleosides

Głowacka

Andrei

Schols

et al. 2017

Archiv der Pharmazie

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A new strategy for the synthesis of N -benzoylated- and N -benzylated N -propargylquinazoline-2,4-diones 30a-d and 31a-d from isatoic anhydride 41 is reported. The alkynes 30a-d and 31a-d were applied in the 1,3-dipolar cycloadditions with azides 27 and 28 to synthesize acyclic 1,2,3-triazole nucleosides. The obtained alkynes and 1,2,3-triazole were evaluated for antiviral activity against a broad range of DNA and RNA viruses. The alkyne 30d showed activity against adenovirus-2 (EC = 8.3 μM), while compounds 37a and 37d were also active toward herpes simplex virus-1 wild-type and thymidine kinase deficient (HSV-1 TK ) strains (EC values in the range of 4.6-13.8 μM). In addition, compounds 30a, 30b, 37b, and 37c exhibited activity toward varicella-zoster virus (VZV) TK and TK strains (EC = 2.1-9.5 μM). The compound 30b proved to be the most selective against VZV and displayed marginal activity against human cytomegalovirus (HCMV). Although the compound 30a had improved anti-HCMV activity, the increase in anti-HCMV activity was accompanied by significant toxicity. Compounds 37a and 37d showed inhibitory effects toward the human T lymphocyte (CEM) cell line (IC = 21 ± 7 and 22 ± 1 μM, respectively), while compound 35 exhibited cytostatic activity toward HMEC-1 cells (IC = 28 ± 2 μM).

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Synthesis and anticancer activity evaluation of new 1,2,3-triazole-4-carboxamide derivatives

Cited by 70 publications

References 21 publications

Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

Reactivity of 2,1‐Benzisoxazole in Palladium‐Catalyzed Direct Arylation with Aryl Bromides

Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3‐Triazole Nucleosides

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