Optimized Synthesis of New N-Mustards Based on 2-Mercaptobenzoxazole Derivatives with Antitumor Activity

Cheptea, Corina; Şunel, Valeriu; Morosanu, Ana Cezarina; Dimitriu, Dan Gheorghe; Dulcescu-Oprea, Mihaela Maria; Angheluta, Mihai-Daniel; Miron, Mihaela; Nechifor, Cristina Delia; Dorohoi, Dana Ortansa; Mălăncuș, R. N.

doi:10.3390/biomedicines9050476

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…For the grafting of the triazole ring on the nucleus of 6-aminopenicillanic acid, it was necessary to activate the carboxylic function of sodium thioacetates (IIIa–IIIc), transforming them into mixed type A anhydrides, able to rapidly and mildly react with the amine group of β-lactamic acid. The pivaloyl chloride is an ideal partner of this transformation, which, for electronic and steric reasons of the three methyl groups at the same carbon atom, facilitates the cleavage of the mixed anhydride at one of the two carbonyls in the desired direction [ 25 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

New Semisynthetic Penicillins Obtained by Coupling of the 6-Aminopenicillanic Acid with 5-Mercapto-1,2,4-triazoles-3,4-disubstituted

Cheptea

Zara

Dimitriu

et al. 2023

IJMS

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In a basic medium, 5-Mercapto-1,2,4-triazoles pass into the thiol form, allowing their transformation into sodium salts, which, in reaction with sodium monochloroacetate, lead to sodium 5-thioacetates of 1,2,4-triazoles-3,4-disubstituted. Sulfur derivatives converted to pivalic mixed anhydrides were used as active forms in the acylation of 6-amino penicillanic acid (6-AP) to obtain new semisynthetic penicillins. They contain in the molecule, together with the β-lactam ring, the nucleus 3-[(5-nitroindazol-1′-yl-methyl)]-4-aryl-5-mercapto-1,2,4-triazole, both contributing to an important antibacterial effect. The structure of the new antibiotics was confirmed by the results of elemental and spectral analysis (FT-IR, 1H- and 13C-NMR). The synthetic penicillins were tested for toxicological action and antibacterial activity and the obtained results were close to those for amoxicillin, the reference drug.

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Section: Resultsmentioning

confidence: 99%

New Semisynthetic Penicillins Obtained by Coupling of the 6-Aminopenicillanic Acid with 5-Mercapto-1,2,4-triazoles-3,4-disubstituted

Cheptea

Zara

Dimitriu

et al. 2023

IJMS

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“…N-mustards—not only M [ 14 ]—played a pivotal role in the development of chemotherapy for cancer [ 40 , 41 , 42 , 43 , 44 , 45 ]. Their development is continuing at a considerable pace [ 46 , 47 , 48 , 49 , 50 , 51 ]. The present study contributes its share to this field.…”

Section: Discussionmentioning

confidence: 99%

Hybrid Molecules of Benzylguanidine and the Alkylating Group of Melphalan: Synthesis and Effects on Neuroblastoma Cells

Bruchelt

Klose

Lischka

et al. 2023

JCM

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The therapy of neuroblastoma relies, amongst other things, on administering chemotherapeutics and radioactive compounds, e.g., the (meta-iodobenzyl)guanidine [131I]mIBG. For special applications (conditioning before stem cell transplantation), busulfan and melphalan (M) proved to be effective. However, both drugs are not used for normal chemotherapy in neuroblastoma because of their side effects. The alkylating drug melphalan contains a (Cl-CH2-CH2-)2N- group in the para-position of the phenyl moiety of the essential amino acid phenylalanine (Phe) and can, therefore, be taken up by virtually all kinds of cells by amino acid transporters. In contrast, mIBG isotopologs are taken up more selectively by neuroblastoma cells via the noradrenaline transporter (NAT). The present study aimed at synthesising and studying hybrid molecules of benzylguanidine (BG) and the alkylating motif of M. Such hybrids should combine the preferential uptake of BGs into neuroblastoma cells with the cytotoxicity of M. Besides the hybrid of BG with the dialkylating group (Cl-CH2-CH2-)2N- bound in the para-position as in M (pMBG), we also synthesised mMBG, which is BG meta-substituted by a (Cl-CH2-CH2-)2N- group. Furthermore, two monoalkylating hybrid molecules were synthesised: the BG para-substituted by a (Cl-CH2-CH2-)NH- group (pM*BG) and the BG meta-substituted by a (Cl-CH2-CH2-)NH- group (mM*BG). The effects of the four new compounds were studied with human neuroblastoma cell lines (SK-N-SH, Kelly, and LS) with regard to uptake, viability, and proliferation by standard test systems. The dialkylating hybrid molecules pMBG and mMBG were at least as effective as M, whereas the monoalkylating hybrid molecules pM*BG and mM*BG were more effective than M. Considering the preferred uptake via the noradrenaline transporter by neuroblastoma cells, we conclude that they might be well suited for therapy.

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“…The data (the dimensionless and the real (between parentheses) variables as well as the measured yield in each experiment) used in 3 2 experiments [35][36][37], are organized in order to optimize the reaction's yield, as shown in Tables 1-3.…”

Section: Optimization Of the Chemical Reactions For Obtaining The Thiosemicarbazides V-viimentioning

confidence: 99%

Optimized Synthesis of New Thiosemicarbazide Derivatives with Tuberculostatic Activity

Popovici

Pavel

Şunel

et al. 2021

IJMS

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Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives’ applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and 1H NMR). A study regarding the optimization of the chemical reactions was made. The performed in vitro biological tests confirmed the tuberculostatic activity of three newly obtained compounds against Mycobacterium tuberculosis.

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Optimized Synthesis of New N-Mustards Based on 2-Mercaptobenzoxazole Derivatives with Antitumor Activity

Cited by 4 publications

References 40 publications

New Semisynthetic Penicillins Obtained by Coupling of the 6-Aminopenicillanic Acid with 5-Mercapto-1,2,4-triazoles-3,4-disubstituted

New Semisynthetic Penicillins Obtained by Coupling of the 6-Aminopenicillanic Acid with 5-Mercapto-1,2,4-triazoles-3,4-disubstituted

Hybrid Molecules of Benzylguanidine and the Alkylating Group of Melphalan: Synthesis and Effects on Neuroblastoma Cells

Optimized Synthesis of New Thiosemicarbazide Derivatives with Tuberculostatic Activity

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