Revealing quinquennial anticancer journey of morpholine: A SAR based review

Arshad, Fatima; Khan, Mohemmed Faraz; Akhtar, Wasim; Alam, Mohammad Mumtaz; Nainwal, Lalit Mohan; Kaushik, Sumit Kumar; Akhter, Mymoona; Parvez, Suhel; Hasan, Syed Misbahul; Shaquiquzzaman, Mohammad

doi:10.1016/j.ejmech.2019.02.015

Cited by 82 publications

(37 citation statements)

References 222 publications

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“…Morpholine (tetrahydro‐1,4‐oxazine) is a heterocycle that is frequently exploited in medicinal chemistry due to its advantageous physicochemical, biological and metabolic properties as well as its mostly facile synthetic routes. Appropriately substituted morpholines have long been known to possess a wide range of biological actions ranging from analgesic, anti‐inflammatory, antioxidant, antiobesity, and antihyperlipidemic to antimicrobial, antineurodegenerative and anticancer activity . The first marketed morpholine‐containing drug was preludin, introduced in therapy for obesity, in 1955 .…”

Section: Introductionmentioning

confidence: 99%

Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules

Kourounakis

Xanthopoulos

Tzara

2019

Medicinal Research Reviews

148

106

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Morpholine is a heterocycle featured in numerous approved and experimental drugs as well as bioactive molecules. It is often employed in the field of medicinal chemistry for its advantageous physicochemical, biological, and metabolic properties, as well as its facile synthetic routes. The morpholine ring is a versatile and readily accessible synthetic building block, it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies. This versatile scaffold, appropriately substituted, possesses a wide range of biological activities. There are many examples of molecular targets of morpholine bioactive in which the significant contribution of the morpholine moiety has been demonstrated; it is an integral component of the pharmacophore for certain enzyme active‐site inhibitors whereas it bestows selective affinity for a wide range of receptors. A large body of in vivo studies has demonstrated morpholine's potential to not only increase potency but also provide compounds with desirable drug‐like properties and improved pharamacokinetics. In this review we describe the medicinal chemistry/pharmacological activity of morpholine derivatives on various therapeutically related molecular targets, attempting to highlight the importance of the morpholine ring in drug design and development as well as to justify its classification as a privileged structure.

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Section: Introductionmentioning

confidence: 99%

Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules

Kourounakis

Xanthopoulos

Tzara

2019

Medicinal Research Reviews

148

106

View full text Add to dashboard Cite

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“…In addition, JS6 does not present solubility issues within the in vitro and in vivo delivery vehicles used to date. The utility of the morpholine group as a popular option for improving water solubility of drug candidates (either as free base or salt form) is well established in drug discovery laboratories (50). Finally, the chemical structure of JS6 provides no obvious toxicological flags (e.g, functional groups associated with metabolic instability or genotoxicity) or promiscuous artifact groups known as pan-assay interference compounds (PAINS) (51).…”

Section: Discussionmentioning

confidence: 99%

The Discovery of a Novel Antimetastatic Bcl3 Inhibitor

Soukupová

Bordoni

Turnham

et al. 2021

Molecular Cancer Therapeutics

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The development of anti-metastatic drugs is an urgent healthcare priority for cancer patients, since metastasis is thought to account for around 90% of cancer deaths. Current antimetastatic treatment options are limited and often associated with poor long-term survival and systemic toxicities. Bcl3, a facilitator protein of the NF-B family, is associated with poor prognosis in a range of tumor types. Bcl3 has been directly implicated in the metastasis of tumor cells, yet is well tolerated when constitutively deleted in murine models, making it a promising therapeutic target. Here we describe the identification and characterization of the first small molecule Bcl3 inhibitor, by employing a virtual drug design and screening approach against a computational model of the Bcl3-NFkB1(p50) protein-protein interaction. From selected virtual screening hits, one compound (JS6) showed potent intracellular Bcl3-inhibitory activity. JS6 treatment led to reductions in Bcl3-NFkB1 binding, tumor colony formation and cancer cell migration in vitro; and tumor-stasis and anti-metastatic activity in vivo, whilst being devoid of overt systemic toxicity. These results represent a successful application of in silico screening in the identification of protein-protein inhibitors for novel intra-cellular targets, and confirm Bcl3 as a potential anti-metastatic target.

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“…BIBR1532 have amide functional group along with naphthalene ring system 34 . The synthesized compounds have morpholine ring system which is more polar characteristics due to presence of oxygen and nitrogen atoms 35 . Similarly, most of the synthesized compounds have carbonyl functionality in the form of ester, amide and thioate esters, which having carbonyl functional group, can have same interactions in binding pocket as BIBR1532 36 .…”

Section: Docking Studymentioning

confidence: 99%

Synthesis, Molecular Docking and Pharmacological Investigation of Heterocyclic Amine Derivatives as Potential Anticancer Agents

Sheikh¹,

Nadeem²,

Alam³

et al. 2021

Preprint

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Cancer is life threatening disease that causes great damage to health worldwide. Studies shown that hypoxia is the major contributor to tumor and cancer development due to overexpression of carbonic anhydrase. To encounter such cells abnormalities, demanding new drugs or novel analogs of currently in use. Therefore, the search for new pharmacoactive moieties with considerable effective activity against such tumors and cancers is needed. The implication of heterocyclic amine and acetamide derivatives well known as chemotherapeutic agents. Heterocyclic amine morpholine was taken as principal products and its new derivatives were synthesized after being designed computationally via molecular docking. A series of some of its new synthetic analogs i.e heterocyclic amine derivatives 1(a-o) were successfully synthesized and screened for their anticancer and carbonic anhydrase inhibitory potential. Most of the compounds showed good results possessing reasonable carbonic anhydrase inhibitory activity particularly compounds 1c, 1d, 1h and 1i showed very reasonable carbonic anhydrase inhibitory activity whereas compound 1h showed maximum inhibition comparable to acetazolamide. Similarly, four of the synthesized compounds showed good anticancer activity particularly compound 1b, 1c, 1h, and 1i showed reasonable, whereas compound 1h have better IC50 value comparable to cisplatin when evaluated via in vitro MTT assay.

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Revealing quinquennial anticancer journey of morpholine: A SAR based review

Cited by 82 publications

References 222 publications

Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules

Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules

The Discovery of a Novel Antimetastatic Bcl3 Inhibitor

Synthesis, Molecular Docking and Pharmacological Investigation of Heterocyclic Amine Derivatives as Potential Anticancer Agents

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