Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro biological activity

Mbaba, Mziyanda; Mabhula, Amanda; Boel, Natasha Marie-Eraine; Edkins, Adrienne L.; Isaacs, Michelle; Hoppe, Heinrich C.; Khanye, Setshaba D.

doi:10.1016/j.jinorgbio.2017.04.014

Cited by 32 publications

(28 citation statements)

References 28 publications

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“…To assess antiplasmodial activity, three-fold serial dilutions of test compounds in culture medium were added to parasite cultures (adjusted to 2% parasitaemia, 1% haematocrit) in 96-well plates and incubated for 48 h. Duplicate wells per compound concentration were used. Parasite lactate dehydrogenase (pLDH) enzyme activity in the individual wells was determined as previously described [35,36].…”

Section: Methodsmentioning

confidence: 99%

New Quinolone-Based Thiosemicarbazones Showing Activity Against Plasmodium falciparum and Mycobacterium tuberculosis

et al. 2019

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Co-infection of malaria and tuberculosis, although not thoroughly investigated, has been noted. With the increasing prevalence of tuberculosis in the African region, wherein malaria is endemic, it is intuitive to suggest that the probability of co-infection with these diseases is likely to increase. To avoid the issue of drug-drug interactions when managing co-infections, it is imperative to investigate new molecules with dual activities against the causal agents of these diseases. To this effect, a small library of quinolone-thiosemicarbazones was synthesised and evaluated in vitro against Plasmodium falciparum and Mycobacterium tuberculosis, the causal agents of malaria and tuberculosis, respectively. The compounds were also evaluated against HeLa cells for overt cytotoxicity. Most compounds in this series exhibited activities against both organisms, with compound 10, emerging as the hit; with an MIC90 of 2 µM against H37Rv strain of M. tuberculosis and an IC50 of 1 µM against the 3D7 strain of P. falciparum. This study highlights quinolone-thiosemicarabazones as a class of compounds that can be exploited further in search of novel, safe agents with potent activities against both the causal agents of malaria and tuberculosis.

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Section: Methodsmentioning

confidence: 99%

New Quinolone-Based Thiosemicarbazones Showing Activity Against Plasmodium falciparum and Mycobacterium tuberculosis

et al. 2019

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“…Novobiocin is an antibiotic that is produced by bacteria called Streptomyces, its inhibitor of the chaperone, heat shock protein 90 (Hsp90) which is responsible for the stabilization of proteins and it is found to be one of the antibiotics that are biological active with anticancer and antimalarial activity when it is incorporated together with other active molecules such as ferrocene [42,43,44].…”

Section: Ferrocene-based Compounds With Antimalaria Activitymentioning

confidence: 99%

“…Novobiocin derivatives containing ferrocene moieties were synthesized and documented by Mbaba et al and they were tested against the 3D7 strain (sensitive) of P. falciparum in vitro (Figure 11). Compounds 28a and 28b exhibited moderate antimalarial activity when compared to other synthesized compounds which exhibited poor antimalarial activity when tested against the 3D7 P. falciparum strain with an inhibition value of 9 nM in vitro [43]. The incorporation of ferrocenyl moiety on the benzamide side of novobiocin resulted in compounds with enhanced biological activity.…”

Section: Ferrocene-based Compounds With Antimalaria Activitymentioning

confidence: 99%

Ferrocene-Based Compounds with Antimalaria/Anticancer Activity

2019

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Malaria and cancer are chronic diseases. The challenge with drugs available for the treatment of these diseases is drug toxicity and resistance. Ferrocene is a potent organometallic which have been hybridized with other compounds resulting in compounds with enhanced biological activity such as antimalarial and anticancer. Drugs such as ferroquine were developed from ferrocene and chloroquine. It was tested in the 1990s as an antimalarial and is still an effective antimalarial. Many researchers have reported ferrocene compounds as potent compounds useful as anticancer and antimalarial agents when hybridized with other pharmaceutical scaffolds. This review will be focused on compounds with ferrocene moieties that exhibit either an anticancer or antimalarial activity.

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“…The in vitro biological evaluation of these compounds against FP‐2 and P. falciparum revealed several compounds with IC 50 values in the low micromolar range. With our interest in ferrocene‐based antimalarial agents coupled with the reported biological activity profile of thiazolidine‐2,4‐dione derivatives, we rationally designed our target compounds by amalgamation of these structural motifs into a single molecule with the intention of generating new compounds (Figure ) with improved pharmacological properties. To the best of our knowledge, there have been no reports focusing on ferrocenyl‐derived thiazolidine‐2,4‐diones as antiprotozoal agents.…”

Section: Introductionmentioning

confidence: 99%

New thiazolidine‐2,4‐dione derivatives combined with organometallic ferrocene: Synthesis, structure and antiparasitic activity

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Tukulula

Isaacs

et al. 2018

Applied Organom Chemis

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Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine‐2,4‐dione framework (TZD‐4) prompted us to explore compounds containing both the thiazolidine‐2,4‐dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene‐based thiazolidine‐2,4‐dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine‐resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD‐4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD‐4 against the P. falciparum parasite. All the synthesised compounds were non‐toxic and often showed >90% viability of the HeLa cell line screened.

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Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro biological activity

Cited by 32 publications

References 28 publications

New Quinolone-Based Thiosemicarbazones Showing Activity Against Plasmodium falciparum and Mycobacterium tuberculosis

New Quinolone-Based Thiosemicarbazones Showing Activity Against Plasmodium falciparum and Mycobacterium tuberculosis

Ferrocene-Based Compounds with Antimalaria/Anticancer Activity

New thiazolidine‐2,4‐dione derivatives combined with organometallic ferrocene: Synthesis, structure and antiparasitic activity

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