Synthesis of carboxyimidamide-substituted benzo[c][1,2,5]oxadiazoles and their analogs, and evaluation of biological activity against Leishmania donovani

Keurulainen, Leena; Heiskari, Mikko; Nenonen, Satu; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Leino, Teppo O.; Yli‐Kauhaluoma, Jari; Jaffe, Charles L.; Kiuru, Paula

doi:10.1039/c5md00119f

Cited by 9 publications

(7 citation statements)

References 21 publications

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“…So, they are attractive candidates for drug self-delivery [ 9 ]. Compared with biodegradable polymers, self-delivery hydrogels based on hydrogelators could change some shortcomings such as adjusting the pore size or networks of polymers, limited loading of drug molecules and functionalizing the polymers with drug molecules [ 10 , 11 ]. Hence, new strategies are needed to conjugate AmB with hydrogels in order to increase its efficacy, reduce its toxicity and to minimize the chance of fungal resistance to AmB.…”

Section: Introductionmentioning

confidence: 99%

Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

Shu

Yang

et al. 2018

R. Soc. open sci.

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The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans. The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.

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Section: Introductionmentioning

confidence: 99%

Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

Shu

Yang

et al. 2018

R. Soc. open sci.

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“…The Bfx 6 and tetrazole 9 intermediates were synthesized using the methodologies reported previously. [51,52] The final compound of the second series, 11 f was obtained in a manner similar to the synthesis of compound 5 n of the first series. However, an aniline derivative containing a hydrogen atom, 13, was used in place of the parent compound containing the fluorine atom, 3 n. The synthetic intermediates 3 n and 12 were synthesized by following previously described procedures.…”

Section: Chemistrymentioning

confidence: 99%

“…Compounds 4, 6, and 9 were synthesized according to previously described methodologies. [50][51][52] The synthetic intermediates 2 a-2 q, 3 a-3 q, 3 n, and 13 were also synthesized as described previously. [47][48][49] The chemical characterization data for all the synthetic intermediates are provided in the Supplementary Material.…”

Section: Experimental Section Chemistrymentioning

confidence: 99%

Benzofuroxan Derivatives as Potent Agents against Multidrug‐Resistant Mycobacterium tuberculosis

et al. 2021

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Tuberculosis (TB) is currently the leading cause of death related to infectious diseases worldwide, as reported by the World Health Organization. Moreover, the increasing number of multidrug-resistant tuberculosis (MDR-TB) cases has alarmed health agencies, warranting extensive efforts to discover novel drugs that are effective and also safe. In this study, 23 new compounds were synthesized and evaluated in vitro against the drug-resistant strains of M. tuberculosis. The compound 6-((3-fluoro-4-thiomorpholinophenyl)carbamoyl)benzo[c][1,2,5] oxadiazole 1-N-oxide (5 b) was particularly remarkable in this regard as it demonstrated MIC 90 values below 0.28 μM against all the MDR strains evaluated, thus suggesting that this compound might have a different mechanism of action. Benzofuroxans are an attractive new class of anti-TB agents, exemplified by compound 5 b, with excellent potency against the replicating and drug-resistant strains of M. tuberculosis.

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“…Nonetheless, a moderate reduction in parasitic load was observed in vivo (Table ). Other research programs have disclosed (benzo)furazan derivatives with antiparasitic activity against T. brucei and L. donovani , but the (benzo)furazan moiety appears to be interchangeable with other heterocycles and the biological activity is modest.…”

Section: Antimicrobialsmentioning

confidence: 99%

Furazans in Medicinal Chemistry

et al. 2021

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Incorporation of heterocycles into drug molecules can enhance physical properties and biological activity. A variety of heterocyclic groups is available to medicinal chemists, many of which have been reviewed in detail elsewhere. Oxadiazoles are a class of heterocycle containing one oxygen and two nitrogen atoms, available in three isomeric forms. While the 1,2,4- and 1,3,4-oxadiazoles have seen widespread application in medicinal chemistry, 1,2,5-oxadiazoles (furazans) are less common. This Review provides a summary of the application of furazan-containing molecules in medicinal chemistry and drug development programs from analysis of both patent and academic literature. Emphasis is placed on programs that reached clinical or preclinical stages of development. The examples provided herein describe the pharmacology and biological activity of furazan derivatives with comparative data provided where possible for other heterocyclic groups and pharmacophores commonly used in medicinal chemistry.

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Synthesis of carboxyimidamide-substituted benzo[c][1,2,5]oxadiazoles and their analogs, and evaluation of biological activity against Leishmania donovani

Cited by 9 publications

References 21 publications

Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

Benzofuroxan Derivatives as Potent Agents against Multidrug‐Resistant Mycobacterium tuberculosis

Furazans in Medicinal Chemistry

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