2-Cyclopropyl-6-phenyl-2,3-dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one

Romain Mustière; Patrice Vanelle; Nicolas Primas

doi:10.3390/m1221

2-Cyclopropyl-6-phenyl-2,3-dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one

Molbank ◽

10.3390/m1221 ◽

2021 ◽

Vol 2021 (2) ◽

pp. M1221

Author(s):

Romain Mustière ◽

Patrice Vanelle ◽

Nicolas Primas

Keyword(s):

Scaffold Hopping ◽

Simple Treatment ◽

Biological Tests

As part of our ongoing scaffold hopping work on antimalarial 2-aminothieno[3,2-d]pyrimidin-4-one scaffold, we explored the dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one as a potential new antimalarial series. Using conditions found in the literature, we obtained 2-cyclopropyl-6-phenyl-2,3-dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one with 93% yield through a simple treatment. It was then characterized by NMR (1H and 13C) and HRMS. Given the structure of this molecule, its aqueous stability was assessed to determine its suitability for biological tests. To our knowledge, this is the first dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one described.

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AutoLinker: Automatic Fragment Linking with Deep Conditional Transformer Neural Networks

10.26434/chemrxiv.12271508.v2 ◽

2020 ◽

Author(s):

Yuyao Yang ◽

Shuangjia Zheng ◽

Shimin Su ◽

Jun Xu ◽

Hongming Chen

Keyword(s):

Neural Networks ◽

Drug Discovery ◽

Drug Design ◽

State Of The Art ◽

The State ◽

Generative Model ◽

Lead Optimization ◽

Scaffold Hopping ◽

Reference Models ◽

Lead Generation

Fragment based drug design represents a promising drug discovery paradigm complimentary to the traditional HTS based lead generation strategy. How to link fragment structures to increase compound affinity is remaining a challenge task in this paradigm. Hereby a novel deep generative model (AutoLinker) for linking fragments is developed with the potential for applying in the fragment-based lead generation scenario. The state-of-the-art transformer architecture was employed to learn the linker grammar and generate novel linker. Our results show that, given starting fragments and user customized linker constraints, our AutoLinker model can design abundant drug-like molecules fulfilling these constraints and its performance was superior to other reference models. Moreover, several examples were showcased that AutoLinker can be useful tools for carrying out drug design tasks such as fragment linking, lead optimization and scaffold hopping.

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New Biological Tests in Patients With Antiphospholipid Antibodies

Case Medical Research ◽

10.31525/ct1-nct03890601 ◽

2019 ◽

Author(s):

Keyword(s):

Antiphospholipid Antibodies ◽

Biological Tests

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Durability of wood and wood-based products. Performance of preservatives as determined by biological tests

10.3403/00659231 ◽

1997 ◽

Keyword(s):

Biological Tests

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Durability of wood and wood-based products. Performance of preservatives as determined by biological tests

10.3403/00963878 ◽

1997 ◽

Keyword(s):

Biological Tests

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Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

Letters in Drug Design & Discovery ◽

10.2174/1570180817999201201113712 ◽

2020 ◽

Vol 17 ◽

Author(s):

Shikha Sharma ◽

Shweta Sharma ◽

Vaishali Pathak ◽

Parwinder Kaur ◽

Rajesh Kumar Singh

Keyword(s):

In Silico ◽

Target Prediction ◽

Drug Repurposing ◽

Docking Studies ◽

Target Protein ◽

Future Perspective ◽

Antibacterial Drug ◽

Scaffold Hopping ◽

Target Proteins ◽

Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

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Investigation of Nutritional Contents, Antioxidant and Immunostimulatory Activities of Aqueous Extract from Laguncularia racemosa Leaves

The Natural Products Journal ◽

10.2174/2210315510666200108105217 ◽

2020 ◽

Vol 10 ◽

Author(s):

Dayane Kelly Dias do Nascimento Santos ◽

Cristiane Moutinho Lagos de Melo ◽

Elivânia Maria da Silva ◽

Vanessa Silva de Almeida ◽

Iranildo José da Cruz Filho ◽

...

Keyword(s):

Antioxidant Activity ◽

Aqueous Extract ◽

Antioxidant Activities ◽

Folk Medicine ◽

Proliferation Index ◽

Laguncularia Racemosa ◽

High Concentration ◽

Popular Medicine ◽

Biological Tests ◽

Phytochemical Profile

Background: One of the four most incident species in mangrove is the Laguncularia racemosa, plant widely used in popular medicine against inflammation and fever. Objective: Here, L. racemosa was investigated in relation to their phytochemical profile, antioxidant activity, citotoxicity, antimicrobial and immunostimulatory effect. Method: Aqueous extract was obtained from leaves of plant, its phytochemical profile was investigated through UPLC method, the antioxidant assays performed were TAA, DPPH, ABTS, nitrite and lipid peroxidation assay. Antimicrobial assays were made using standard strains. For all biological tests were used mice splenocytes and from these cell cultures were measured cytotoxicity, proliferation index and cytokines production. Results: Laguncularia racemosa leaves showed the presence of ions, proteins, carbohydrates, vitamins and high concentration of phenolic compounds. Antioxidant activities were promoted by aqueous extract, especially in DPPH and NO assays. Extract in 6 µg/mL did not induce significant cell death, stimulated the cell proliferation and the IL-4 production. Moreover, decreases of proinflammatory cytokines IFN-γ, TNF-α and IL-6 were found. Conclusion: The presence of essential nutrients, significant antioxidant activity and immune stimulation confirm the use of this plant in folk medicine against inflammation.

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Analogues of the cholecystokinin octapeptide modified in the central part of the molecule

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19911963 ◽

1991 ◽

Vol 56 (9) ◽

pp. 1963-1970 ◽

Cited By ~ 3

Author(s):

Jan Hlaváček ◽

Václav Čeřovský ◽

Jana Pírková ◽

Pavel Majer ◽

Lenka Maletínská ◽

...

Keyword(s):

Amino Acid ◽

Biological Activities ◽

Point Of View ◽

Biologically Active ◽

Side Chain ◽

Amino Acid Residues ◽

Cholecystokinin Octapeptide ◽

Biological Tests ◽

Biological Potency ◽

Biologically Active Conformation

In a series of analogues of the cholecystokinin octapeptide (CCK-8) the amino acid residues were gradually modified by substituting Gly by Pro in position 4, Trp by His in position 5, Met by Cle in position 6, or the Gly residue was inserted between Tyr and Met in positions 2 and 3 of the peptide chain, and in the case of the cholecystokinin heptapeptide (CCK-7) the Met residues were substituted by Nle or Aib. These peptides were investigated from the point of view of their biological potency in the peripheral and central region. From the results of the biological tests it follows that the modifications carried out in these analogues and in their Nα-Boc derivatives mean a suppression of the investigated biological activities by 2-3 orders of magnitude (at a maximum dose of the tested substance of 2 . 10-2 mg per animal).This means that a disturbance of the assumed biologically active conformation of CCK-8, connected with a considerable decrease of the biological potency of the molecule, takes place not only after introduction of the side chain into its centre (substitution of Gly4), but also after the modification of the side chains of the amino acids or by extension of the backbone in further positions around this central amino acid.

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Anti-Tumor and Anti-Inflammatory Activity In Vivo of Apodanthera congestiflora Cogn. (Cucurbitaceae)

Pharmaceutics ◽

10.3390/pharmaceutics13050743 ◽

2021 ◽

Vol 13 (5) ◽

pp. 743

Author(s):

Geovana F. G. Silvestre ◽

Renally P. Lucena ◽

Genil D. Oliveira ◽

Helimarcos N. Pereira ◽

Jhonatta A. B. Dias ◽

...

Keyword(s):

Inflammatory Activity ◽

Phytochemical Investigation ◽

Significant Toxicity ◽

Biological Tests ◽

Ehrlich's Carcinoma ◽

Anti Inflammatory ◽

Pharmacological Potential ◽

First Time ◽

Anti Tumor Activity

This work aimed to carry out a study of Apodanthera congestiflora by investigating its chemical composition and pharmacological potential. From the dichloromethane phase (Dic-Ac) of the A. congestiflora stems, three compounds were identified: cayaponoside C5b (Ac-1), cabenoside C (Ac-2) and fevicordin C2 glucoside (Ac-3), being last identified for the first time as a natural product. These compounds were obtained by chromatographic methods and their structures were elucidated by means of spectroscopic analysis of IR, MS and NMR. In the quantification of Dic-Ac, it was possible to observe the presence of 7% of cayaponoside C5b. Dic-Ac showed significant toxicity for in vivo tests, with macroscopic and biochemical changes. The anti-inflammatory activity of Dic-Ac was investigated using the paw edema model. A decrease in inflammatory signs was observed in the first 5 h and the most effective dose in reducing edema with was 7.5 mg kg−1 (66.6%). Anti-tumor activity of Dic-Ac was evaluated by Ehrlich’s carcinoma model, which showed inhibition rate of 78.46% at 15 mg kg−1 dosage. The phytochemical investigation, together with the biological tests carried out in this study, demonstrated that A. congestiflora is a promising species in the search for therapeutics, since it contains substances with high pharmacological potential in its composition.

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