Mannich bases of 1,2,4‐triazole‐3‐thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies

Milosev, M.; Jakovljević, Katarina; Stanojković, Tatjana; Matić, Ivana Z.; Perović, Milka; Tešić, Vesna; Kanazir, Selma; Mladenović, Milan; Rodić, Marko V.; Leovac, Vukadin M.; Trifunović, Snežana; Marković, Violeta

doi:10.1111/cbdd.12920

Cited by 20 publications

(8 citation statements)

References 50 publications

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“…This method allows the synthesis of the desired compound at an excellent yield. Synthesis of 1,2,4-triazole 16 was performed by the cyclocondensation of compound 15 in an aqueous solution of sodium hydroxide under refluxing conditions with 80% yield, as described previously [ 30 ]. 2-Amino-1,3,4-thiadiazole 17 was synthesized with a 71% yield after recrystallization from EtOH following a procedure previously described [ 31 ], which involved the treatment of starting compound 15 with concentrated sulfuric acid at room temperature.…”

Section: Resultsmentioning

confidence: 99%

Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments

et al. 2021

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Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC50 (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.

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Section: Resultsmentioning

confidence: 99%

Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments

et al. 2021

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“…6a with lower lipophilicity than ManDMPTAd didn’t stimulate immune response, while 6b and 6c with higher log p values have stronger immunostimulating potency. Adamantyl, adamantylethyl and C 12 alkyl groups were connected to the L-Ala-D- iso Gln pharmacophore over 1,2,3-triazole moiety, which was obtained by optimized CuI-catalyzed azide/alkyne cycloaddition (CuAAC) [ 9 , 16 , 29 , 30 ]. Target compounds ManDMPTAd, 6a , 6b and 6c were synthesized with good overall yields.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents

Peroković

Car

Bušljeta

et al. 2022

IJMS

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Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP) is the smallest peptidoglycan fragment able to trigger an immune response by activating the NOD2 receptor. Structural modification of MDP can lead to analogues with improved immunostimulating properties. The aim of this work was to prepare mannosylated desmuramyl peptides (ManDMP) containing lipophilic triazole substituents to study their immunomodulating activities in vivo. The adjuvant activity of the prepared compounds was evaluated in the mouse model using ovalbumin as an antigen and compared to the MDP and referent adjuvant ManDMPTAd. The obtained results confirm that the α-position of D-isoGln is the best position for the attachment of lipophilic substituents, especially adamantylethyl triazole. Compound 6c exhibited the strongest adjuvant activity, comparable to the MDP and better than referent ManDMPTAd.

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“…In vitro Biological Evaluation of 1,2,4-triazole Mannich Base role of compounds in the biological process especially antimicrobial and other beneficial activities that will be found in the Mannich bases [11][12][13][14][15][16] . Mannich bases in medicinal chemistry have multiple advantages with heterocycles like anticancer, antiviral, anti-inflammatory, and antioxidant 17,18 .…”

Section: Orginal Articlementioning

confidence: 99%

In vitro Biological Evaluation of 1,2,4-triazole Mannich Base

Rafaat,

Karatepe,

Keser

et al. 2023

Bio. Med. Tar. Jour.

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Biological evaluation of a 1,2,4-triazole mannich base that has been synthesized for interesting behavior in medicinal chemistry, so it’s interesting to synthesize triazole derivatives and investigate their biological properties to evaluate their capacity in medicine. The aim of this study evaluate the antimicrobial, anticancer, and antioxidant activities of a 1,2,4-triazole Mannich base derivative and its power in the treatment of diseases. For antimicrobial activity four bacterial strains and one fungal strain based on the agar disc diffusion. While used two cancer cell lines for anticancer activity which are known as Hep-G2 and MCF-7; the antioxidant activity of the compound used three different radical species include OH•, ABTS•+, and DPPH•, and also determine the antioxidant activity of the compound after extracting vitamins A, C, E, and MDA in the S. cerevisiae yeast cell by HPLC. The results of this study show the positive role of a derivative 1,2,4-triazole mannich base as antimicrobial and antiradical assays, particularly when treated with C. albicans and OH• radical that significantly reduced growth of the fungal and the radical compared to others. In addition, it didn’t exhibit any cytotoxicity to reduce both cancer cell lines. In conclusion, the compound's ability is different from one assay to another, increasing its concentration efficiency affects the radical scavenging, and inhibits microorganism growth.

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Mannich bases of 1,2,4‐triazole‐3‐thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies

Cited by 20 publications

References 50 publications

Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments

Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments

Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents

In vitro Biological Evaluation of 1,2,4-triazole Mannich Base

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