Sulfated Derivatives of Arabinogalactan and Their Anticoagulant Activity

Abstract The thrombin binding aptamer (TBA) possesses promising antiproliferative properties. However, its development as an anticancer agent is drastically impaired by its concomitant anticoagulant activity. Therefore, suitable chemical modifications in the TBA sequence would be required in order to preserve its antiproliferative over anticoagulant activity. In this paper, we report structural investigations, based on circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR), and biological evaluation of four pairs of enantiomeric heterochiral TBA analogues. The four TBA derivatives of the d-series are composed by d-residues except for one l-thymidine in the small TT loops, while their four enantiomers are composed by l-residues except for one d-thymidine in the same TT loop region. Apart from the left-handedness for the l-series TBA derivatives, CD and NMR measurements have shown that all TBA analogues are able to adopt the antiparallel, monomolecular, ‘chair-like’ G-quadruplex structure characteristic of the natural D-TBA. However, although all eight TBA derivatives are endowed with remarkable cytotoxic activities against colon and lung cancer cell lines, only TBA derivatives of the l-series show no anticoagulant activity and are considerably resistant in biological environments.

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Synthesis, Docking, and In Vitro Anticoagulant Activity Assay of Hybrid Derivatives of Pyrrolo[3,2,1-ij]Quinolin-2(1H)-one as New Inhibitors of Factor Xa and Factor XIa

Molecules ◽

10.3390/molecules25081889 ◽

2020 ◽

Vol 25 (8) ◽

pp. 1889 ◽

Cited By ~ 1

Author(s):

Nadezhda Novichikhina ◽

Ivan Ilin ◽

Anna Tashchilova ◽

Alexey Sulimov ◽

Danil Kutov ◽

...

Keyword(s):

Anticoagulant Activity ◽

Factor Xa ◽

Coagulation Factor ◽

Coagulation Factors ◽

Protein Targets ◽

Ic50 Value ◽

Anticoagulant Drugs ◽

Factor Xia ◽

Derivatives Of

Coagulation factor Xa and factor XIa are proven to be convenient and crucial protein targets for treatment for thrombotic disorders and thereby their inhibitors can serve as effective anticoagulant drugs. In the present work, we focused on the structure–activity relationships of derivatives of pyrrolo[3,2,1-ij]quinolin-2(1H)-one and an evaluation of their activity against factor Xa and factor XIa. For this, docking-guided synthesis of nine compounds based on pyrrolo[3,2,1-ij]quinolin-2(1H)-one was carried out. For the synthesis of new hybrid hydropyrrolo[3,2,1-ij]quinolin-2(1H)-one derivatives, we used convenient structural modification of both the tetrahydro- and dihydroquinoline moiety by varying the substituents at the C6,8,9 positions. In vitro testing revealed that four derivatives were able to inhibit both coagulation factors and three compounds were selective factor XIa inhibitors. An IC50 value of 3.68 μM for was found for the best factor Xa inhibitor and 2 μM for the best factor XIa inhibitor.

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THE ANTICOAGULANT ACTION IN BLOOD OF SULPHATED DERIVATIVES OF LAMINARIN

Canadian Journal of Biochemistry and Physiology ◽

10.1139/o55-068 ◽

1955 ◽

Vol 33 (4) ◽

pp. 545-552 ◽

Cited By ~ 11

Author(s):

W. W. Hawkins ◽

A. N. O'Neill

Keyword(s):

Anticoagulant Activity ◽

Brown Seaweeds ◽

Ether Derivative ◽

Anticoagulant Action ◽

Sulphamic Acid ◽

Derivatives Of ◽

Harmful Effects

Laminarin, a polysaccharide from brown seaweeds, has been sulphated to produce compounds which show anticoagulant activity in blood in vivo. Derivatives of sulphamic acid were more active than simple sulphate esters, although the amount of sulphate also affected the activity. When tested in rats one sulphated β-aminoethyl ether derivative was 40–50% as potent as heparin, and one ester about 30%. Tests with rats and dogs indicated no harmful effects in the doses used.

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Synthesis and anticoagulant activity of 1-aryl derivatives of tetrahydroisoquinolines

Pharmaceutical Chemistry Journal ◽

10.1007/s11094-006-0128-1 ◽

2006 ◽

Vol 40 (7) ◽

pp. 363-366 ◽

Cited By ~ 5

Author(s):

V. A. Glushkov ◽

K. A. Arapov ◽

O. N. Minova ◽

N. G. Ismailova ◽

B. Ya. Syropyatov ◽

...

Keyword(s):

Anticoagulant Activity ◽

Derivatives Of

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Synthesis and Pharmacological Evaluation of Novel Coumarin Derivatives

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1908 ◽

2020 ◽

Vol 11 (1) ◽

pp. 865-874

Author(s):

Sanaryh Mohammed Al-awad ◽

Leaqaa Abdalredha raheem ◽

Ausama Ayob Jaccob

Keyword(s):

Antioxidant Activity ◽

Anticoagulant Activity ◽

Lethal Dose ◽

Biological Behavior ◽

Coumarin Derivatives ◽

Anti Cancer ◽

Anti Oxidant ◽

Interesting Class ◽

Derivative Products ◽

Derivatives Of

The current work focuses on new architecture, synthesis of coumarin-oxadiazole hybrid derivative products as both these (coumarin ring and oxadiazole) have a wide variety of biological behavior, Compounds containing the nucleus of coumarin (2H-1-benzopyran-2-one) are an interesting class of hetero cycles which hold an important role in the field of natural ingredients and synthetic organic chemistry. It has been exciting medicinal chemists to study native coumarins or synthetic analogs for their application for decades. And they can be further modified to synthesize more effective and potent drugs. Compounds have been characterized by spectrophotometry of physicochemical properties and their structures verified by infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H-NMR) Such new derivatives of coumarinyl-oxadiazole was qualified to estimate the lethal dose, anticancer, anticoagulant and antioxidant activity. Their pharmacological properties depend on their pattern of substitution, compound S4F proved significant anticoagulant activity in concentration (50, 100, 200 mg/ml) similar for heparin, and monitor the coagulation effect on plasma, while compound S4CO give significant anticancer activity against MCF-7 a breast cancer cell. Specific compounds have strong antioxidants with the effective action of radical scavengers; the S4Cl compound with IC50 1.49 is the most potent antioxidant activity note. Basically, all the formulations tested reported satisfactory behavior. The review shows that varieties of coumarin derivatives have synthesized and shown anti-cancer, antioxidant and anti-coagulant potentials. These derivatives synthesis and its biological assay can be further modified in the future to improve the anti-cancer, anti-oxidant and anticoagulant potentials of the versatile coumarin nucleus.

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