Benzoxazines as new human topoisomerase I inhibitors and potential poisons

Foto, Egemen; Özen, Çigdem; Zilifdar, Fatma; Tekiner-Gülbaş, Betül; Yıldız, İlkay; Akı-Yalçın, Esin; Dırıl, Nuran; Yalçın, İsmail

doi:10.1007/s40199-019-00315-x

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…Benzoxazines, such as 1,4-benzoxazin-3-ones and 2,4-Dihydroxy-1,4-benzoxazin-3-one ( Figure 3 F), present in maize [ 77 ], wheat and rye [ 54 ] are a group of molecules showing antimicrobial and antitumor activity [ 78 , 79 ]. In a recent work, Foto et al demonstrated that benzoxazines and their derivatives act as hTopIB inhibitors, interfering with the binding of the enzyme to the DNA [ 55 ]. According to relaxation assay and EMSA experiments, the DNA-binding capacity of hTopoIB is reduced by benzoxazines in a dose-dependent concentration, suggesting a possible use of these molecules as a lead compound to develop new drugs for cancer treatment.…”

Section: Natural Compounds With In Vitro and In Vivo Activity On Htopibmentioning

confidence: 99%

Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB

Ottaviani

Iacovelli

Fiorani

et al. 2021

IJMS

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Natural products are widely used as source for drugs development. An interesting example is represented by natural drugs developed against human topoisomerase IB, a ubiquitous enzyme involved in many cellular processes where several topological problems occur due the formation of supercoiled DNA. Human topoisomerase IB, involved in the solution of such problems relaxing the DNA cleaving and religating a single DNA strand, represents an important target in anticancer therapy. Several natural compounds inhibiting or poisoning this enzyme are under investigation as possible new drugs. This review summarizes the natural products that target human topoisomerase IB that may be used as the lead compounds to develop new anticancer drugs. Moreover, the natural compounds and their derivatives that are in clinical trial are also commented on.

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Section: Natural Compounds With In Vitro and In Vivo Activity On Htopibmentioning

confidence: 99%

Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB

Ottaviani

Iacovelli

Fiorani

et al. 2021

IJMS

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“…Scheme 7 Synthetic pathway for functionalized 2-oxo-benzo [1,4]oxazines Dhafer and his co-workers have reviewed the synthesis and anti-microbial, antitubercular, ntioxidant, anticancer and anti-inflammatory effects of these synthesized oxazines [82].Çigdem Özen et-al. Have studied substituted 1,4-oxazine as DNA topoisomerase I inhibitors which might acts as a novel constructs for future anticancer agent designs [83].…”

Section: Oxazines Drives From Phenolesmentioning

confidence: 99%

Synthesis and pharmaceutical applications of Oxazine compounds derived from Pyronic, Salicylic, Antharanilic acids and Phenols

Al-Ajely¹

2021

Int. J. Sci. Res. Arch.

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It is well known from FDA reports that More than 75% of the heterocyclic compounds are drugs and 90 of heterocyclic compounds are cancer drugs. The nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. Most drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties, More over heterocyclic compounds are important class of organic chemistry due to their widely spread in nature. Also there are many route for their action and many mechanistic pathways for their preparation and different metabolic actions. This comes from the easily building or removal of any functional group within the molecules. Changing just on group cause to change the metabolic pathway of the drug action and site of attack of the desired target accordingly. This great characteristic value make them much more important in drug discovery programs of many researchers and also encouraged us and drew attentions of other researchers to develop new ways for their synthesis. As a result different pharmacological and medical applications. Oxazie compounds are sub branch of heterocyclic compounds. These compounds having two hetero atoms, Oxygen and nitrogen within their structures make them much more important toward therapeutic studies. We are here in our investigation will focus on the methodologies and the therapeutic action of the titled compounds as well as other various applications.

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“…Therefore, the appearance of relaxed topoisomers along with residual supercoiled form indicates the partial activity of topoisomerase I and thus its inhibition by the test compounds. In a previous studies, it was said that the compounds poisoning topoisomerase caused the formation of nick bands in such gel appearances, while the formation of Supercoiled bands was said to be caused by catalytic inhibitors that bound to either DNA or enzyme 40,41 .…”

Section: Dna Topoisomerase I Assaymentioning

confidence: 99%

Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison

Çevik

Sağlık

Osmaniye

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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In this study, some benzimidazole-oxadiazole derivatives were synthesised and tested for their in vitro anticancer activities on five cancer cell lines, including HeLa, MCF7, A549, HepG2 and C6. Their structures were elucidated by IR, 1 H-NMR, 13 C-NMR, 2 D-NMR and HRMS spectroscopic methods. Among all screened compounds; 5a, 5b, 5d, 5e, 5k, 5l, 5n and 5o exhibited potent selective cytotoxic activities against various tested cancer cell lines. Especially, compounds 5l and 5n exhibited the most antiproliferative activity than Hoechst 33342 and doxorubicin against HeLa cell line, with IC 50 of 0.224 ± 0.011 mM and 0.205 ± 0.010 mM, respectively. Furthermore, these potent lead cytotoxic agents were evaluated in terms of their inhibition potency against Topoisomerase I and it was determined that selected compounds inhibited the Topoisomerase I. Docking studies were performed and probable interactions in the DNA-Topo I enzyme complex was determined.

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Benzoxazines as new human topoisomerase I inhibitors and potential poisons

Cited by 11 publications

References 30 publications

Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB

Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB

Synthesis and pharmaceutical applications of Oxazine compounds derived from Pyronic, Salicylic, Antharanilic acids and Phenols

Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison

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