Chemotherapeutic Applications of Folate Prodrugs: A Review

2021 ◽  
Vol 19 (8) ◽  
pp. 99-112
Author(s):  
Yasser Fakri Mustafa
Keyword(s):  
Biological Activity ◽  
Drug Design ◽  
Small Molecules ◽  
Significant Interaction ◽  
Active Drug ◽  
Folate Receptor ◽  
The Other ◽  
Technological Innovations ◽  
Drug Molecule ◽  
Drug Conjugates

Several techniques to assisting in the drug design and discovery stages have been developed during the last several decades. The bulk of these techniques aimed to find novel chemical entities that had the greatest significant interaction with the targeted receptors or enzymes while providing the least degree of risk of unwanted interactions. This approach, on the other hand, is time-consuming and expensive, as it requires the screening of thousands of molecules for biological activity, with only one making it to market. The prodrug strategy, in which the active drug molecule is disguised by a promoiety to change its undesirable characteristics, is one of the most appealing and promising methods. The folate receptor (FR)-targeted systems may also open the path for more advanced drug conjugates, especially because this receptor is now being targeted by a variety of technological innovations, including nanoparticles, small molecules, and protein-based technologies, resulting in a wealth of experience in the discipline.

Small molecule drug conjugates (SMDCs): an emerging strategy for anticancer drug design and discovery

2021 ◽  
Vol 45 (12) ◽  
pp. 5291-5321
Author(s):  
Tarun Kumar Patel ◽  
Nilanjan Adhikari ◽  
Sk. Abdul Amin ◽  
Swati Biswas ◽  
Tarun Jha ◽  
...  
Keyword(s):  
Drug Design ◽  
Anticancer Drug ◽  
Small Molecule ◽  
Chemotherapeutic Agents ◽  
Drug Molecule ◽  
Lysosomal Ph ◽  
Small Molecule Drug ◽  
Drug Conjugates ◽  
Small Molecule Drugs ◽  
Tumor Environment

Mechanisms of how SMDCs work. Small molecule drugs are conjugated with the targeted ligand using pH sensitive linkers which allow the drug molecule to get released at lower lysosomal pH. It helps to accumulate the chemotherapeutic agents to be localized in the tumor environment upon cleaving of the pH-labile bonds.

A FACILE SYNTHESIS AND REACTIONS OF AMINO SELENOLO[2,3-b]PYRIDINE CARBOXYLATE

2015 ◽  
Vol 12 (1) ◽  
pp. 3910-3918 ◽  
Author(s):  
Dr Remon M Zaki ◽  
Prof Adel M. Kamal El-Dean ◽  
Dr Nermin A Marzouk ◽  
Prof Jehan A Micky ◽  
Mrs Rasha H Ahmed
Keyword(s):  
Biological Activity ◽  
Carbonyl Compounds ◽  
Mass Spectra ◽  
The Other ◽  
Pyridine Derivatives ◽  
Facile Synthesis ◽  
High Biological Activity ◽  
Basic Hydrolysis ◽  
Pyridine Carboxylate ◽  
Hydrolysis Of

 Incorporating selenium metal bonded to the pyridine nucleus was achieved by the reaction of selenium metal with 2-chloropyridine carbonitrile 1 in the presence of sodium borohydride as reducing agent. The resulting non isolated selanyl sodium salt was subjected to react with various α-halogenated carbonyl compounds to afford the selenyl pyridine derivatives 3a-f  which compounds 3a-d underwent Thorpe-Ziegler cyclization to give 1-amino-2-substitutedselenolo[2,3-b]pyridine compounds 4a-d, while the other compounds 3e,f failed to be cyclized. Basic hydrolysis of amino selenolo[2,3-b]pyridine carboxylate 4a followed by decarboxylation furnished the corresponding amino selenolopyridine compound 6 which was used as a versatile precursor for synthesis of other heterocyclic compound 7-16. All the newly synthesized compounds were established by elemental and spectral analysis (IR, 1H NMR) in addition to mass spectra for some of them hoping these compounds afforded high biological activity.

Broad Assessment of Bioactivity of a Collection of Spiroindane Pyrrolidines Through “Cell Painting”

2020 ◽  
Author(s):  
Zarko Boskovic ◽  
Manvendra Singh ◽  
Zachary Pearson ◽  
Nathan Garza
Keyword(s):  
Biological Activity ◽  
Small Molecules ◽  
Functional Groups ◽  
Organelle Morphology

A collection of small molecules has been synthesized by composing photo-cycloaddition, C-H functionalization, and N-capping strategies. Multidimensional biological fingerprints of molecules comprising this collection have been recorded as changes in cell and organelle morphology. This untargeted, phenotypic approach allowed for a broad assessment of biological activity to be determined. Reproducibility and the magnitude of measured fingerprints revealed activity of several treatments. Reactive functional groups, such as imines, dominated the observed activity. Two non-reactive candidate compounds with distinct bioactivity fingerprints were identified, as well.

Effect of C6-Volatiles on Bioluminescent Plant Pathogens

HortScience ◽  
1998 ◽  
Vol 33 (3) ◽  
pp. 557d-557
Author(s):  
Jennifer Warr ◽  
Fenny Dane ◽  
Bob Ebel
Keyword(s):  
Biological Activity ◽  
Bacterial Growth ◽  
Xanthomonas Campestris ◽  
Plant Pathogens ◽  
Genetically Engineered ◽  
The Other ◽  
Computer Assisted ◽  
Signal Molecules ◽  
Low Concentrations

C6 volatile compounds are known to be produced by the plant upon pathogen attack or other stress-related events. The biological activity of many of these substances is poorly understood, but some might produce signal molecules important in host–pathogen interactions. In this research we explored the possibility that lipid-derived C6 volatiles have a direct effect on bacterial plant pathogens. To this purpose we used a unique tool, a bacterium genetically engineered to bioluminesce. Light-producing genes from a fish-associated bacterium were introduced into Xanthomonas campestris pv. campestris, enabling nondestructive detection of bacteria in vitro and in the plant with special computer-assisted camera equipment. The effects of different C6 volatiles (trans-2 hexanal, trans-2 hexen-1-ol and cis-3 hexenol) on growth of bioluminescent Xanthomonas campestris were investigated. Different volatile concentrations were used. Treatment with trans-2 hexanal appeared bactericidal at low concentrations (1% and 10%), while treatments with the other volatiles were not inhibitive to bacterial growth. The implications of these results with respect to practical use of trans-2 hexanal in pathogen susceptible and resistant plants will be discussed.

Naphthoquinone Derivatives Isolated from Plants: Recent Advances in Biological Activity

2020 ◽  
Vol 20 (19) ◽  
pp. 2019-2035
Author(s):  
Esmaeil Sheikh Ahmadi ◽  
Amir Tajbakhsh ◽  
Milad Iranshahy ◽  
Javad Asili ◽  
Nadine Kretschmer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Biological Activity ◽  
Small Molecules ◽  
Anticancer Activity ◽  
Clinical Significance ◽  
Phase Ii ◽  
Biological Activities ◽  
Phase Ii Clinical Trials ◽  
Naturally Occurring ◽  
The Subject

Naturally occurring naphthoquinones (NQs) comprising highly reactive small molecules are the subject of increasing attention due to their promising biological activities such as antioxidant, antimicrobial, apoptosis-inducing activities, and especially anticancer activity. Lapachol, lapachone, and napabucasin belong to the NQs and are in phase II clinical trials for the treatment of many cancers. This review aims to provide a comprehensive and updated overview on the biological activities of several new NQs isolated from different species of plants reported from January 2013 to January 2020, their potential therapeutic applications and their clinical significance.

scholarly journals Therapeutic Advances in Oncology

2021 ◽  
Vol 22 (4) ◽  
pp. 2008
Author(s):  
Jinsha Liu ◽  
Priyanka Pandya ◽  
Sepideh Afshar
Keyword(s):  
Small Molecules ◽  
New Technologies ◽  
Treatment Options ◽  
Current Treatment ◽  
Bispecific Antibodies ◽  
Gene Therapies ◽  
Therapeutic Modalities ◽  
The Past ◽  
Drug Conjugates ◽  
Novel Targets

Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.

Mastication of Rubber. II. Interpolymerization of Natural Rubber and Neoprene on Cold Milling

1956 ◽  
Vol 29 (2) ◽  
pp. 427-437
Author(s):  
D. J. Angier ◽  
W. F. Watson
Keyword(s):  
Free Radicals ◽  
Natural Rubber ◽  
Small Molecules ◽  
The Other ◽  
Polymer Molecules ◽  
Commercially Important ◽  
The Individual ◽  
Cold Mill ◽  
General Method ◽  
Butadiene Styrene

Abstract The softening of elastomers on cold milling results from scission of the polymer molecules by the applied shearing forces. The ruptured chains are free radicals, which can undergo mutual combination, interaction with oxygen and various additives, and branching (grafting) on to other polymer molecules. A general method of producing graft and block interpolymers between elstomers is therefore indicated, namely, to cold-mill the polymers together in the absence of small molecules which can terminate the polymeric radicals in order that the radicals may cross-terminate or graft onto the polymer molecules of the other type. A survey of several pairs of the commercially important elastomers, natural rubber, butadiene-styrene, Neoprene, and butadiene-acrylonitrile, has shown that cold milling does effect interlinking. Detailed results for the rubber-Neoprene system are reported in this communication. Experimental verification of polymer interlinking was obtained from the solubility properties of the milled elastomers. Cold milling of Neoprene under nitrogen produces gel, whereas of natural rubber does not, but the milling of mixtures gives gels containing natural rubber. Also, the solubilities and precipitation of the milled mixtures cannot be accounted for by these properties of the individual polymers. Finally, Neoprene-natural rubber mixtures, after and not before cold-milling, can be cross-linked by magnesium oxide, with rubber bound into the vulcanizate.

scholarly journals Thiol-sensitive sites in cell adhesion. Decreased entry of SH-binding reagents into attached BHK cells

1982 ◽  
Vol 208 (2) ◽  
pp. 473-478 ◽  
Author(s):  
D D McAbee ◽  
F Grinnell
Keyword(s):  
Cell Adhesion ◽  
Small Molecules ◽  
Cell Spreading ◽  
The Other ◽  
Bhk Cells ◽  
Sh Groups ◽  
Nitrobenzoic Acid ◽  
Cytoplasmic Proteins ◽  
Adhesion Process ◽  
Suspended Cells

Studies were carried out to learn more about the critical SH groups involved in cell spreading. Pretreatment of suspended baby hamster kidney (BHK) cells with 3 mM-iodoacetate or iodoacetamide for 10 min at 4 degrees C completely inhibited the ability of the cells to spread on fibronectin-coated substrata. If, however, BHK cells were permitted to attach and spread before being treated with the SH-binding reagents, and then harvested by trypsinization and assayed for spreading on fibronectin-coated substrata, there was no inhibition of cell spreading. The extent of prior attachment required before the cells became insensitive to the SH-binding reagents was tested and was found to occur early during the cell adhesion process, before any cell spreading was observed. In analytical experiments, there did not appear to be any difference in the total number of SH groups between suspended or spread cells as determined with 5,5′-dithiobis-(2-nitrobenzoic acid). The uptake of radiolabelled iodoacetate into intact spread cells, however, was found to be 3.5 times less than that found with suspended cells. On the other hand, the distribution of incorporated radioactivity into suspended and spread cells was similar. Most of the radioactivity (approximately 70%) was incorporated into small molecules (e.g. glutathione and cysteine), less (approximately 20%) was incorporated into cytoplasmic proteins, and the least incorporation (approximately 10%) was into the cell cytoskeleton. The data are interpreted to indicate there is a decreased permeability of spread cells to the SH-binding reagents.

scholarly journals Isolasi dan Identifikasi Senyawa Fenolik dari Kulit Akar Tumbuhan Artocarpus Dadah Miq 63-74

2015 ◽  
Vol 4 (2) ◽  
pp. 205
Author(s):  
Indarto Indarto
Keyword(s):  
Biological Activity ◽  
Phenolic Compounds ◽  
Ir Spectroscopy ◽  
The Other ◽  
Flash Chromatography ◽  
Rare Plant ◽  
Isolation And Purification ◽  
Phenolic Group ◽  
The Village ◽  
Murine Leukemia

Artocarpus plant  dadah  Miq.  is one of the species of Artocarpus of the Moraceae family that belongs to a rare plant in nature. This plant is known as the main source of phenolic derivative compound that is flavone compound  in  or  tri-oxygenated and terisoprenilasi in C-3 position ,  and also known as the main source of phenolic compound derived flavonoids, aryl-benzofuran, stilbenoid and xanthane flavonoida, which have biological activity as promoters antitumor, antibacterial, antifungal, antiimflamatori, antikanker and others. This study aimed to isolate and identify the phenolic compounds contained in plant  A .  dadah obtained from the village of Purwoasri, North Metro District, Metro City, Lampung Province. Research stages include collection and sample preparation and extraction, isolation, and purification of compounds using KCV method, flash chromatography  , KKG, and TLC, while the identification of compounds is performed using ultraviolet-visible (UV-VIS) and infrared (IR) spectroscopy. In the present study, three compounds were isolated, one of which was estimated to be flavonoid compounds based on UV-VIS and IR spectra data which also had high activity against murine leukemia P-388 cells with IC 50  3.1 μg / mL. Based on the IR spectral data for the other two compounds there is a -OH uptake in the region of 3200-3500 cm -1, C = C aromatic uptake in the area of 1600-1400 cm -1 , so it is estimated that both compounds are phenolic group compounds.Tumbuhan Artocarpus dadah Miq.merupakan salah satu spesies Artocarpus dari famili Moraceae yang termasuk tumbuhan langka di alam. Tumbuhan ini dikenal sebagai sumber utama senyawa turunan fenolik yaitu senyawa flavon di atau tri-oksigenasi dan terisoprenilasi pada posisi C-3, dan juga dikenal sebagai sumber utama senyawa fenolik turunan flavonoid, aril-benzofuran, stilbenoid dan santon turunan flavonoida, yang memiliki aktivitas biologi sebagai promotor antitumor, antibakteri, antifungal, antiimflamatori, antikanker dan lain-lain.Penelitian ini bertujuan untuk mengisolasi dan mengidentifikasi senyawa fenolik yang terkandung dalam tumbuhan A. dadah yang diperoleh dari desa Purwoasri, Kecamatan Metro Utara, Kota Metro, Provinsi Lampung.Tahapan penelitian yang dilakukan meliputi pengumpulan dan persiapan sampel kemudian ekstraksi, isolasi, dan pemurnian senyawa menggunakan metode KCV, kromatografi flash, KKG, dan KLT, sedangkan identifikasi senyawa dilakukan menggunakan spektroskopi ultraungu-tampak (UV-VIS) dan inframerah (IR). Pada penelitian ini telah berhasil diisolasi tiga senyawa, yang salah satunya diperkirakan senyawa flavonoid berdasarkan data spektrum UV-VIS dan IR yang juga memiliki aktivitas tinggi terhadap sel murine leukemia P-388 dengan IC50 3,1 μg/mL. Berdasarkan data spektrum IR untuk dua senyawa yang lain terdapat serapan –OH pada daerah 3200-3500 cm-1, serapan C=C aromatik di daerah 1600-1400 cm-1, sehingga diperkirakan kedua senyawa tersebut merupakan senyawa golongan fenolik.

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