Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine − synthesis, cytostatic, antiviral and antioxidative studies

Perković, Ivana; Tršinar, Sara; Žanetić, Jelena; Kralj, Marijeta; Martin-Kleiner, Irena; Balzarini, Jan; Hadjipavlou‐Litina, Dimitra; Katsori, A.‐M.; Zorc, Branka

doi:10.3109/14756366.2012.663366

Cited by 24 publications

(18 citation statements)

References 30 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MCF‐7 cells were sensitive to 15 of the 24 tested compounds, namely, 5 a – d , 2 d , 2 e , 4 a , 4 c – e , and 6 a – d . Similar results were obtained in our previous studies with various PQ derivatives . On the other hand, HepG2 cells were very robust and only responded towards 4 d and compounds from subclass 5 .…”

Section: Resultssupporting

confidence: 90%

“…Such observations prompted us, and others, to design and prepare novel derivatives of known antimalarial drugs and evaluate their cytostatic potential . Our efforts have been focused on primaquine (PQ), which is an old drug with many flaws (e.g., induction of hemolytic anemia in individuals lacking glucose‐6‐phosphate dehydrogenase, quick metabolism, degradation to inactive carboxyprimaquine, altering the treatment outcome in dependence of CYP 2D6 enzyme activity) but is currently the only available Plasmodium hypnozoitocide .…”

Section: Introductionmentioning

confidence: 99%

“…Our efforts have been focused on primaquine (PQ), which is an old drug with many flaws (e.g., induction of hemolytic anemia in individuals lacking glucose‐6‐phosphate dehydrogenase, quick metabolism, degradation to inactive carboxyprimaquine, altering the treatment outcome in dependence of CYP 2D6 enzyme activity) but is currently the only available Plasmodium hypnozoitocide . We previously showed that various PQ derivatives of amides, ureas, bis‐ureas, semicarbazides, and acylsemicarbazide‐type derivatives possessed significant cytostatic activity against a panel of cancer cell lines or high selectivity towards the breast adenocarcinoma cell line (MCF‐7) . On the other hand, cytostatic agents of different classes, including histone deacetylase (HDAC) inhibitors, have been shown to exert antiplasmodial activity .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

et al. 2018

Self Cite

View full text Add to dashboard Cite

We report the synthesis of SAHAquines and related primaquine (PQ) derivatives. SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and PQ, an antimalarial drug with low antiproliferative activity. The preparation of SAHAquines is simple, cheap, and high yielding. It includes the following steps: coupling reaction between primaquine and a dicarboxylic acid monoester, hydrolysis, a new coupling reaction with O‐protected hydroxylamine, and deprotection. SAHAquines 5 a–d showed significant reduction in cell viability. Among the three human cancer cell lines (U2OS, HepG2, and MCF‐7), the most responsive were the MCF‐7 cells. The antibodies against acetylated histone H3K9/H3K14 in MCF‐7 cells revealed a significant enhancement following treatment with N‐hydroxy‐N′‐{4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}pentanediamide (5 b). Ethyl (2E)‐3‐({4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}carbamoyl)prop‐2‐enoate (2 b) and SAHAquines were the most active compounds against both the hepatic and erythrocytic stages of Plasmodium parasites, some of them at sub‐micromolar concentrations. The results of our research suggest that SAHAquines are promising leads for new anticancer and antimalarial agents.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The following drugs were used: NSAIDs (ketoprofen, Ket, indomethacin, Ind, fenoprofen, Fen, diclofenac, Dic, ibuprofen, Ibu), 35,37,[46][47][48] antihyperlipemic (gemfibrozil, Gem), 48,57,58 estrogens (estradiol benzoate, EB, estradiol valerate, EV), 59,60 uricosuric (probenecid, Pro) 36 and antimalarian drug primaquine, PQ. 56 Structures of the drugs used in preparation of polymer-drug conjugates are presented in Figure 1.…”

Section: Synthesis Of Polymer-drug Conjugatesmentioning

confidence: 99%

“…35,37,[46][47][48]56,[57][58][59][60] With amino acids (glycine and β-alanine) or ethylenediamine derivatives 67 and 70 with additional functional group useful for further derivatization or binding to polymers were obtained and used in preparation of the conjugates with a spacer between polymer and drug. 46,58 More than twenty polymer-drug conjugates were prepared, which differed in the polymer type, average molecular mass, bound drug, type of polymer-drug bond (ester, amide or carbamate), type of spacer and drugloading.…”

Section: Synthesis Of Polymer-drug Conjugatesmentioning

confidence: 99%

Benzotriazole as a Synthetic Auxiliary

Zorc¹,

Džolić²,

Butula³

2012

Croat. Chem. Acta

Self Cite

View full text Add to dashboard Cite

Abstract. Benzotriazole is a very useful synthetic auxiliary with versatile applications in organic chemistry. We have used benzotriazole in the synthesis of various heterocyclic compounds (benzoxazine, quinazoline, triazinetrione, hydantoin, oxadiazine and diazepane derivatives), amino acid derivatives, carbamates, ureas, semicarbazides, carbazides, sulfonylureas, sulfonylcarbazides, hydantoic acids, nonsteroidal antiinflammatory drug (NSAID) and primaquine derivatives, polymer-drug and thiomer-drug conjugates. The results have been published in more than 30 papers and here we give an overview of all syntheses. (doi: 10.5562/cca2124)

show abstract

Synthesis and Antimicrobial Evaluation of Novel Derivatives of Semicarbazide and 1,2,4‐triazole

Pachuta‐Stec

Biernasiuk

Malm

et al. 2017

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

Reaction of phenoxyacetic acid hydrazide with isocyanate was used to the synthesis of new semicarbazide derivatives. Cyclization of these compounds in a 2% aqueous solution of sodium hydroxide led to formation of 1,2,4‐triazole‐3‐one. The chemical structure of synthesized compounds was confirmed by elemental analysis and spectroscopic methods (1H and 13C NMR). On the basis of the NMR, spectra were found that cyclic compounds 1,2,4‐triazole exist in the ‐one form. Moreover, all derivatives were examined for their in vitro activity against some species of bacteria. New compounds presented mild or moderate antimicrobial activity only against reference Gram‐positive bacteria. Two derivatives (one semicarbazide and one triazole) showed bactericidal or bacteriostatic activity.

show abstract

Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine − synthesis, cytostatic, antiviral and antioxidative studies

Cited by 24 publications

References 30 publications

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

Benzotriazole as a Synthetic Auxiliary

Synthesis and Antimicrobial Evaluation of Novel Derivatives of Semicarbazide and 1,2,4‐triazole

Contact Info

Product

Resources

About