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Correlation between polar surface area and bioferroelectricity in DNA and RNA nucleobases

Yam SC, Zain SM, Sanghiran Lee V, Chew KH

Eur Phys J E Soft Matter, 2018 Jul 18;41(7):86.
PMID: 30014219 DOI: 10.1140/epje/i2018-11696-5

We have performed computational molecular modelling to study the polarization switching and hysteresis loop behaviours of DNA and RNA nucleobases using the PM3 semi-empirical quantum mechanical approaches. All the nucleobases: adenine (A), thymine (T), guanine (G), cytosine (C), and uracil (U) were modelled. Our study indicates that all the nucleobases exhibit a zero-field polarization due to the presence of polar atoms or molecules such as amidogen and carbonyl. The shape of polarization P versus an applied electric field E hysteresis loop is square, implying typical ferroelectrics behaviour. The total energy U as a function of an applied electric field E exhibits a butterfly-like loop. The presence of zero-field polarization and ferroelectrics hysteresis loop behaviours in nucleobases may support the hypothesis of the existence of bioferroelectricity in DNA and RNA. We also found an interesting relationship between the minimum electric field required for switching [Formula: see text] and the ratio of the topological polar surface area (TPSA) to the total surface area (TSA) of a nucleobase. In particular, the [Formula: see text] of a nucleobase is inversely proportional to the TPSA/TSA ratio. This work may provide useful information for understanding the possible existence of ferroelectricity in biomaterials.

Matched MeSH terms: Purines/chemistry*
1,3,5-Triazine-based analogues of purine: from isosteres to privileged scaffolds in medicinal chemistry

Lim FP, Dolzhenko AV

Eur J Med Chem, 2014 Oct 6;85:371-90.
PMID: 25105925 DOI: 10.1016/j.ejmech.2014.07.112

Purines can be considered as the most ubiquitous and functional N-heterocyclic compounds in nature. Structural modifications of natural purines, particularly using isosteric ring systems, have been in the focus of many drug discovery programs. Fusion of 1,3,5-triazine ring with pyrrole, pyrazole, imidazole, 1,2,3-triazole or 1,2,4-triazole results in seven bicyclic heterocyclic systems isosteric to purine. Application of the isosterism concept for the development of new compounds with therapeutic potential in areas involving purinergic regulation or purine metabolism led to significant advances in medicinal chemistry of the azolo[1,3,5]triazines. These 1,3,5-triazine-based purine-like scaffolds significantly increase level of molecular diversity and allow covering chemical space in the important areas of medicinal chemistry. Some of these azolo[1,3,5]triazine systems have become privileged scaffolds in the development of inhibitors of various kinases, phosphodiesterase, xanthine oxidase, and thymidine phosphorylase, antagonists of adenosine and corticotropin-releasing hormone receptors, anticancer and antiviral agents.

Matched MeSH terms: Purines/metabolism; Purines/pharmacology; Purines/chemistry*
Fulltext Effects of N6-benzylaminopurine and indole acetic acid on in vitro shoot multiplication, nodule-like meristem proliferation and plant regeneration of Malaysian bananas (Musa spp)

Philip Sipen, Michael R Davey

Trop Life Sci Res, 2012;23(2):67-80.
MyJurnal

Different concentrations of N6-benzylaminopurine (BAP) and indole acetic acid (IAA) in Murashige and Skoog based medium were assessed for their effects on shoot multiplication, nodule-like meristem proliferation and plant regeneration of the Malaysian banana cultivars Pisang Mas, Pisang Nangka, Pisang Berangan and Pisang Awak. BAP at 1-14 mg L-1 with or without 0.2 mg L-1 IAA, or BAP at 7-14 mg L-1with the same concentration of IAA, was evaluated for shoot multiplication from shoot tips and the proliferation of nodule-like meristems from scalps, respectively. Plant regeneration from scalps was assessed using 1 mg L-1BAP and 0.2 mg L-1 IAA separately, or a combination of these two growth regulators. Data on shoot multiplication, the proliferation of nodule-like meristems with associated plant regeneration were recorded after 30 days of culture. A maximum of 5 shoots per original shoot tip was achieved on medium supplemented with BAP at 5 mg L-1 (Pisang Nangka), 6 mg L-1(Pisang Mas and Pisang Berangan), or 7 mg L-1 (Pisang Awak), with 0.2 mg L-1 IAA. BAP at 11 mg L-1 with 0.2 mg L-1 IAA induced the most highly proliferating nodule-like meristems in the four banana cultivars. Plant regeneration from scalps was optimum in all cases on medium containing 1 mg L-1 BAP and 0.2 mg L-1 IAA. This is the first report on the successful induction of highly proliferating nodule-like meristems and plant regeneration from scalps of the Malaysian banana cultivars Pisang Mas, Pisang Nangka, Pisang Berangan and Pisang Awak.

Matched MeSH terms: Purines
Fulltext Does baricitinib reduce mortality and disease progression in SARS-CoV-2 virus infected patients? A systematic review and meta analysis

Manoharan S, Ying LY

Respir Med, 2022 Oct;202:106986.
PMID: 36150282 DOI: 10.1016/j.rmed.2022.106986

BACKGROUND: There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim of the current systematic review and meta-analysis was to evaluate the efficacy of baricitinib in COVID-19 patients.
METHODS: Databases like ScienceDirect, PubMed/Medline, Publons, Google Scholar and other sources like ClinicalTrials.gov, Cochrane, medRxiv, Research Square and reference lists were thoroughly searched.
RESULTS: Fifteen (15) articles which met the inclusion criteria were qualitatively and quantitatively analysed. Based on Cochrane and Newcastle-Ottawa Scale (NOS) risk of bias (RoB) analyses, 14/15 articles are grouped as high-quality. Meta-analyses revealed that randomised control trials (RCTs) and non-randomised control trials (nRCTs) statistically significantly reduced the mortality rate in COVID-19 patients, with a risk ratio (RR) in the fixed-effect model was RR = 0.64 [95% CI: 0.51 to 0.79; p

Matched MeSH terms: Purines
Encapsulation of in vitro Plectranthus amboinicus (Lour.) Spreng. shoot apices for propagation and conservation

Arumugam G, Sinniah UR, Swamy MK, Lynch PT

3 Biotech, 2019 Aug;9(8):298.
PMID: 31328080 DOI: 10.1007/s13205-019-1831-4

This investigation demonstrates an efficient method of propagation, short-term conservation, and germplasm exchange for Plectranthus amboinicus (Lour.) Spreng. encapsulated propagules. In vitro-derived shoot apices (shoot tips and nodal segments) which showed 100% survival on MS medium supplemented with 0.4 mg/L 6-benzylaminopurine were selected for encapsulation studies. Shoot apices measuring about 3-5 mm in size showed the ability to break the beads and exhibited 100% survival and regrowth. The combination of 3% (w/v) sodium alginate and 100 mM CaCl2 was found to be ideal for forming uniformally spherical beads, and successive preservation of encapsulated shoot apices into plantlets. The encapsulated shoot tips were relatively more effective than the nodal segments in terms of shoot growth and multiplication. Encapsulated shoot tips retained the ability to regrow (63.3%) for up to 40 days when maintained at 4 °C. Encapsulated shoot tips effectively converted into plantlets on agar medium (78%) and peat moss (58%) under in vitro conditions. Encapsulated shoot tips on agar medium showed a higher shoot regeneration (9.91 ± 0.15 shoots per explant) ability than the peat moss (5.71 ± 0.34 shoots per explant), while the highest rooting (12.16 ± 0.23 roots per explant) was observed on peat moss. Thus, calcium alginate encapsulation holds latent qualities that could be explored to develop a future alternative method of propagation, short-term storage and germplasm distribution for elite genotypes of Plectranthus sp.

Matched MeSH terms: Purines
Identification of thioketone analogues of sildenfil using gas chromatography-mass spectrometry

Man CN, Noor NM, Lajis R

J Chromatogr A, 2011 Sep 28;1218(39):7055-60.
PMID: 21872876 DOI: 10.1016/j.chroma.2011.08.037

Sildenafil analogues have been found adulterated in herbal preparations and food products that claim to have natural aphrodisiacs. In this study, a gas chromatography-mass spectrometry (GC-MS) assay was developed for the screening and identification of thioketone analogues of sildenafil. Thiopyrazolopyrimidine, a precursor or a cleavage product of thioketone analogue, exhibited characteristic fragment ions of m/z 328 and m/z 299 was found to be the best marker to screen the presence of general thioketone analogues. Identification by GC-MS assay was rapid and specific as all the studied thioketones showed characteristic mass fragmentations including their intact molecular ions. The developed GC-MS assay had successfully identified thiosildenafil, thiohomosildenafil and thiodimethylsildenafil in herbal preparation and food products.

Matched MeSH terms: Purines/isolation & purification; Purines/chemistry
Identification of sildenafil, tadalafil and vardenafil by gas chromatography-mass spectrometry on short capillary column

Man CN, Nor NM, Lajis R, Harn GL

J Chromatogr A, 2009 Nov 20;1216(47):8426-30.
PMID: 19853256 DOI: 10.1016/j.chroma.2009.10.016

Sildenafil and its analogues (tadalafil and vardenafil) are phosphodiesterase type 5 inhibitors used in the treatment of male erectile dysfunction. Some dietary supplements, herbal preparations and food products which claim to enhance male sexual function have been found to be adulterated with these drugs. In this study, a gas chromatograph-mass spectrometer (GC-MS) assay was developed for identification of the drugs. In addition to good and short chromatographic separation that can be achieved within 6 min by using a short 10 m capillary column, no prior sample clean-up before GC-MS analysis was required, thus making this assay a cost saving and rapid method. Furthermore, the assay is specific as the identification of sildenafil, tadalafil and vardenafil were done by detection of molecular ions; m/z 474, 389 and 488, [corrected] respectively, and several other characteristic ions resulted from the mass fragmentation of individual molecules. Using our currently developed assay, sildenafil and its analogues were successfully identified in food and herbal matrices.

Matched MeSH terms: Purines/analysis; Purines/chemistry
Fulltext Callus cell proliferation from broccoli leaf slice using IBA and BAP in vitro culture: Its biochemical and antioxidant properties

Sharif Hossain AB, Haq I, Ibrahim NA, Aleissa MS

Data Brief, 2016 Mar;6:214-20.
PMID: 26862562 DOI: 10.1016/j.dib.2015.11.061

Plant tissue or cell culture keeps a significant role in micro-propagation in the plant production industry. Combination of 6-Benzylaminopurine (BAP) and other plant growth regulators like 1-Naphthaleneacetic acid (NAA) or Indole-3-acetic acid (IAA) or indole-3-butyric acid (IBA) was used in the most of the research in tissue culture. The study was carried out to investigate the optimization of the concentration of IBA and BAP combination (0, 0.25, 0.50, 1.0, 1.50, 2.0, 2.5, 3.0 and 3.5 mg/l) for the root, callus and leaf proliferation from the leaf cutting slice. The highest number (6.75) of root proliferation was observed in the concentration of 2.0 mg/l IBA+0.25 mg/l BAP combination. The callus initiation was found in the concentration of IBA 1.0-3.5 mg/l+BAP 1.0-2.0 mg/l. However, the highest callus weight was observed at the concentration of IBA 1.5 mg/l+BAP 1.0 mg/l combination than other combination of concentrations. Positively leaf initiation and formation was better in the concentration of IBA 1-3.5 mg/l+BAP 1.0-2.0 mg/l combination. In addition, the 2,2-diphenyl-2-picrylhydarzyl (DPPH) free radical scavenging potential was higher (70.1%) in leaves extract than in callus extracts (46.3%) at the concentration of 10 mg/ml though both extracts had lower DPPH free radical scavenging activity compared to the positive control, vitamin C and BHT. Theresults conclude that the optimum concentration was IBA 1.5 mg/l+BAP 1.0 mg/l combination to produce callus cell proliferation and concentration of 2.0 mg/l IBA+0.25 mg/l BAP combination was the optimum for root proliferation of broccoli in vitro.

Matched MeSH terms: Purines
Fulltext Equilibrative Nucleoside Transporter 2: Properties and Physiological Roles

Naes SM, Ab-Rahim S, Mazlan M, Abdul Rahman A

Biomed Res Int, 2020;2020:5197626.
PMID: 33344638 DOI: 10.1155/2020/5197626

Equilibrative nucleoside transporter 2 (ENT2) is a bidirectional transporter embedded in the biological membrane and is ubiquitously found in most tissue and cell types. ENT2 mediates the uptake of purine and pyrimidine nucleosides and nucleobase besides transporting a variety of nucleoside-derived drugs, mostly in anticancer therapy. Since high expression of ENT2 has been correlated with advanced stages of different types of cancers, consequently, this has gained significant interest in the role of ENT2 as a potential therapeutic target. Furthermore, ENT2 plays critical roles in signaling pathway and cell cycle progression. Therefore, elucidating the physiological roles of ENT2 and its properties may contribute to a better understanding of ENT2 roles beyond their transportation mechanism. This review is aimed at highlighting the main roles of ENT2 and at providing a brief update on the recent research.

Matched MeSH terms: Purines
Fulltext Influence of N6-Benzyladenine and Sucrose on In Vitro Direct Regeneration and Microrhizome Induction of Kaempferia parviflora Wall. Ex Baker, An Important Ethnomedicinal Herb of Asia

Labrooy C, Abdullah TL, Stanslas J

Trop Life Sci Res, 2020 Apr;31(1):123-139.
PMID: 32963715 DOI: 10.21315/tlsr2020.31.1.8

Kaempferia parviflora is an ethnomedicinally important plant. Conventional propagation of K. parviflora is hindered by slow growth rate, long dormancy periods and dual use of rhizomes for seeds as well as marketable produce. In our study, we developed a promising dual-phase micropropagation protocol to increase number of plantlets, survivability, biomass and quality plantlets for mass production. Multiple shoot regeneration was found most successful on Murashige and Skoog (MS) media supplemented with 35.52 μM N6-benzyladenine (BA) in terms of highest number of shoots (22.4 ± 1.84), leaves (29.27 ± 1.30), and roots (17.8 ± 1.72) per explant. High survivability was observed with an acclimatisation percentage of 100% in sterile perlite medium. This method was shown to be preferable compared to conventional propagation in terms of propagation time and number of plantlets. Regenerated in vitro plantlets were then successfully induced to form microrhizomes in MS media with an optimal concentration of 6% (w/v) sucrose. Increase in microrhizome biomass (35.7 ± 2.59 g per flask), number of microrhizomes (5.2 ± 0.78), shoots (8.5 ± 1.58) and roots (8.5 ± 1.58) were observed for this treatment. This investigation successfully highlights the manipulation of single factors in short time frame to produce a simple and efficient alternative propagation method for K. parviflora.

Matched MeSH terms: Purines
In vitro regeneration and comparison of phenolic content, antioxidant and antityrosinase activity of in vivo and in vitro grown asparagus officinalis

Esmaeili AK, Rosna Mat Taha, Mohajer S, Banisalam B

Sains Malaysiana, 2016;45:373-381.

Asparagus officinalis as a valuable medicinal plant has a low multiplication rate using the conventional methods. This study was carried out to establish an efficient in vitro propagation protocol and also to compare some biological activities of in vivo and in vitro grown Asparagus. The nodal explants were cultured on MS medium supplemented with different concentrations of 6-benzylaminopurine (BAP) and 1-Naphthaleneacetic acid (NAA) or kinetin (Kn) and Indolebutyric acid (IBA), under light and dark conditions. After 6 weeks of culture, the highest percentage (100%) of callus formation was found in 17 of treatments under dark condition and 3 treatments under light condition. Also between the two groups of hormones, Kn +IBA showed better results in promoting callus formation. The highest average number of shoots (4.25) of size 4 mm or more per explant, formed under dark condition using 1.5 mg/L BAP mixed with 0.05 mg/L NAA. Rooting was best induced in shoots excised from shoot cultures which were proliferated on MS medium supplemented with an optimal concentration of 0.4 mg/L IBA (2 roots per explant). In the second part of the study, the extracts of in vivo and in vitro grown plants as well as callus tissue were tested for their total phenolic and flavonoid content, antioxidant and antityrosinase activities, using two different extraction solvents (methanol and hexane). The methanol extract of in vivo grown plants showed a significantly higher amount of total phenolic and flavonoid content. The antioxidant activity of tested samples followed this order; in vivo plant > callus > in vitro plant.

Matched MeSH terms: Purines
Desiccation tolerance in Phaleria macrocarpa Embryonic Axes

Ahmed Asrity S, Tsan FY, Ding P, Syed Aris S

Sains Malaysiana, 2014;43:1471-1475.

Phaleria macrocarpa seeds are rapidly killed with desiccation to moisture content (MC) below 20%. Desiccation tolerance of their embryonic axes was studied for storage and germplasm conservation purposes. Embryonic axes were extracted aseptically from fresh seeds obtained from fully ripe fruits in a horizontal laminar air flow cabinet. They were then desiccated under aseptic condition for periods ranging from 0-8 h. For each desiccation treatment, embryonic axes were drawn randomly for the determination of MC according to ISTA, electrolyte leakage and proliferation on Murashige and Skoog (MS) media supplemented with 1 mg/l 6-benzylaminopurine (BAP) and 1 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D). The results obtained from this study indicated that the embryonic axes could tolerate dehydration down to 13.6% with desiccation for 8 h while retaining relatively high viability of 76.7%. This was supported by only gradual increment of electrolyte leakage with the desiccated embryonic axes. All non-desiccated embryonic axes with MC of 52.5% were capable to grow into normal plantlets in vitro but dehydration to MC of 36.0% and further down to 13.6% generally resulted in callus formation with up to 16.7% of the embryonic axes while at least 60.0% of the other embryonic axes were still capable to proliferate as normal plantlets in vitro.

Matched MeSH terms: Purines
In vitro shoot regeneration from leaf explants of kenaf (Hibiscus cannabinus L.)

Samanthi P, Mohd Puad A, Suhaimi N, Kumar S, Nor Aini A

Sains Malaysiana, 2013;42:1505-1510.

Kenaf (Hibiscus cannabinus L.) is a versatile plant with multiuse ranging from animal feed to a wide variety of biocomposite products such as pulp and paper and fibre reinforce plastic. Therefore genetically improved planting materials are needed to tailor made requirement of the industry. Thus, development of plant regeneration through callus is important for in vitro genetic manipulation of kenaf. Currently development of successful genetic transformation of kenaf is through in planta transformation means. In vitro shoot regeneration was conducted using leaf explants from varieties V36 and G4 treated to three different combinations of N6 Benzyl adenine (BA) and Indole-3-butyric acid (IBA). High percentage of healthy callus induction was produced in MS medium supplemented with combination of 1.5 mgL-1 BA and 0.5 mgL-1 IBA. In addition 68.7% plant regeneration was obtained in MS medium supplemented with 0.3 mgL-1 GA3. All plantlets produced roots in hormone free medium. There was no significant difference among varieties in terms of callus induction (number of callus) and plant regeneration (number of plantlets). This protocol is useful to be used for the development of gene transformation protocol of kenaf through callus.

Matched MeSH terms: Purines
Fulltext Micropropagation of an exotic ornamental plant, Calathea crotalifera, for production of high quality plantlets

Rozali SE, Rashid KA, Taha RM

ScientificWorldJournal, 2014;2014:457092.
PMID: 25136669 DOI: 10.1155/2014/457092

A successful protocol was established for micropropagation in two selected varieties of exotic ornamental plants, Calathea crotalifera. The effects of different sterilization techniques, explant type, and the combination and concentration of plant growth regulators on shoots induction were studied. The axillary shoot buds explants sprouted from rhizomes in soil free conditions showed high induction rate of shoots with lowest contamination percentage when treated with combination of 30% (v/v) NaOCl, 70% (v/v) ethanol, and 0.3% (w/v) HgCl2. In the present study, the highest number of multiple shoots was obtained in MS basal medium supplemented with 3.5 mg/L 6-Benzylaminopurine (BAP), 1.0 mg/L 1-Naphthaleneacetic acid (NAA), 3% sucrose, and 6 g/L plant agar for both varieties and was used as multiplication medium. Microshoots were highly induced when the young shoot bud explants were incised longitudinally prior subculture. Chlorophyll analysis was studied to test the effects of activated charcoal and L-glutamine on reduction of necrosis problem. The maximum roots induction was recorded on MS medium supplemented with 1.0 mg/L 1-Naphthaleneacetic acid (NAA) compared to indolebutyric acid (IBA). The complete regenerated plantlets were successfully acclimatized in the soilless medium under greenhouse condition. This is the first report of rapid mass propagation for C. crotalifera.

Matched MeSH terms: Purines/pharmacology
Cyclic compression of chondrocytes modulates a purinergic calcium signalling pathway in a strain rate- and frequency-dependent manner

Pingguan-Murphy B, El-Azzeh M, Bader DL, Knight MM

J Cell Physiol, 2006 Nov;209(2):389-97.
PMID: 16883605

Mechanical loading modulates cartilage homeostasis through the control of matrix synthesis and catabolism. However, the mechanotransduction pathways through which chondrocytes detect different loading conditions remain unclear. The present study investigated the influence of cyclic compression on intracellular Ca2+ signalling using the well-characterised chondrocyte-agarose model. Cells labelled with Fluo4 were visualised using confocal microscopy following a period of 10 cycles of compression between 0% and 10% strain. In unstrained agarose constructs, not subjected to cyclic compression, a subpopulation of approximately 45% of chondrocytes exhibited spontaneous global Ca2+ transients with mean transient rise and fall times of 19.4 and 29.4 sec, respectively. Cyclic compression modulated global Ca2+ signalling by increasing the percentage of cells exhibiting Ca2+ transients (population modulation) and/or reducing the rise and fall times of these transients (transient shape modulation). The frequency and strain rate of compression differentially modulated these Ca2+ signalling characteristics providing a potential mechanism through which chondrocytes may distinguish between different loading conditions. Treatment with apyrase, gadolinium and the P2 receptor blockers, suramin and basilen blue, significantly reduced the percentage of cells exhibiting Ca2+ transients following cyclic compression, such that the mechanically induced upregulation of Ca2+ signalling was completely abolished. Thus cyclic compression appears to activate a purinergic pathway involving the release of ATP followed by the activation of P2 receptors causing a combination of extracellular Ca2+ influx and intracellular Ca2+ release. Knowledge of this fundamental cartilage mechanotransduction pathway may lead to improved therapeutic strategies for the treatment of cartilage damage and disease.

Matched MeSH terms: Purines/metabolism*
Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure-Based Drug Design

Luna G, Dolzhenko AV, Mancera RL

ChemMedChem, 2019 04 03;14(7):714-743.
PMID: 30740924 DOI: 10.1002/cmdc.201900034

Xanthine oxidase (XO) is the enzyme responsible for the catabolism of purines and their conversion into uric acid. XO is thus the target for the treatment of hyperuricemia and gout. For more than 50 years the only XO inhibitor drug available on the market was the purine analogue allopurinol. In the last decade there has been a resurgence in the search for new inhibitors of XO, as the activity of XO and hyperuricemia have also been associated with a variety of conditions such as diabetes, hypertension, and other cardiovascular diseases. In recent years the non-purine inhibitor febuxostat was approved in Europe and the USA for the treatment of hyperuricemia. This drug was followed by another XO inhibitor called topiroxostat. This review discusses the molecular structures and activities of the multiple classes of inhibitors that have been developed since the discovery of allopurinol, with a brief review of the molecular interactions between inhibitors and XO active site residues for the most important molecules. The challenges ahead for the discovery of new inhibitors of XO with novel chemical structures are discussed.

Matched MeSH terms: Purines/chemistry
Fulltext Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review

Nur Husna SM, Tan HT, Mohamud R, Dyhl-Polk A, Wong KK

Ther Adv Med Oncol, 2018;10:1758835918808509.
PMID: 30542378 DOI: 10.1177/1758835918808509

Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recently, three emerging and vital groups of proteins are targeted by SMIs for breast cancer treatment, namely cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP) and phosphoinositide 3-kinase (PI3K). Several of these inhibitors have been approved for the treatment of breast cancer patients or progressed into late-stage clinical trials. Thus, modeling from these successful clinical trials, as well as their limitations, is pivotal for future development and trials of other inhibitors or therapeutic regimens targeting breast cancer patients. In this review, we discuss eight recently approved or novel SMIs against CDK4/6 (palbociclib, ribociclib and abemaciclib), PARP (olaparib, veliparib and talazoparib), and PI3K (buparlisib and alpelisib). The mechanisms of action, series of clinical trials and limitations are described for each inhibitor.

Matched MeSH terms: Purines
Fulltext In Vitro Responses of Plant Growth Factors on Growth, Yield, Phenolics Content and Antioxidant Activities of Clinacanthus nutans (Sabah Snake Grass)

Haida Z, Nakasha JJ, Hakiman M

Plants (Basel), 2020 Aug 14;9(8).
PMID: 32823824 DOI: 10.3390/plants9081030

Clinacanthus nutans, commonly known as Sabah snake grass, is one of the more important medicinal plants in Malaysia's herbal industry. C. nutans has gained the attention of medical practitioners due to its wide range of bioactive compounds responsible for various biological activities, such as anti-cancer, anti-venom and anti-viral activities. Due to its high pharmacological properties, the species has been overexploited to meet the demands of the pharmaceutical industry. The present study was conducted to establish a suitable in vitro culture procedure for the mass propagation of C. nutans. Murashige and Skoog (MS) basal medium, supplemented with different types of cytokinins, auxins, basal medium strength and sucrose concentrations, were tested. Based on the results, a full-strength MS basal medium supplemented with 12 µM 6-benzylaminopurine (BAP) and 30 g/L sucrose was recorded as the best outcome for all the parameters measured including the regeneration percentage, number of shoots, length of shoots, number of leaves and fresh weight of leaves. In the analysis of the phenolics content and antioxidant activities, tissue-cultured leaf extracts assayed at 100 °C exhibited the highest phenolic content and antioxidant activities. The propagation of C. nutans via a plant tissue culture technique was recorded to be able to produce high phenolic contents as well as exhibit high antioxidant activities.

Matched MeSH terms: Purines
Induction, Subculture Cycle, and Regeneration of Callus in Safed Musli (Chlorophytum borivilianum) using Different Types of Phytohormones

Nakasha JJ, Sinniah UR, Kemat N, Mallappa KS

Pharmacogn Mag, 2016 Jul;12(Suppl 4):S460-S464.
PMID: 27761075

BACKGROUND: Chlorophytum borivilianum is an industrially valued medicinal crop. Propagation through seeds is not feasible because of low germination percentage and long dormancy period. Therefore, callus culture and plant regeneration can be an alternative to improve this crop production. Also, callus can serve as an alternative source of bioactive compounds.
OBJECTIVE: To evaluate the effect of different phytohormones on callus induction, subculture cycle, and regeneration studies of callus in C. borivilianum.
MATERIALS AND METHODS: Young shoot buds of C. borivilianum were inoculated on Murashige and Skoog medium fortified with 3% sucrose and different concentrations (0, 1, 5, 10, and 15 mg/L) of either naphthalene acetic acid or 2,4-dichlorophenoxyacetic acid or indole-3-acetic acid and callus induction was evaluated up to four subcultures cycles. Shoot regeneration from callus was studied on Murashige and Skoog media fortified with 6-benzylaminopurine andkinetin or thidiazuron at varied levels (0, 0.5, 1, 2, and 3 mg/L). Microshoots were rooted on Murashige and Skoog media supplemented with 1.0 mg/L indole-3-butyric acid and plantlets were acclimatized before transferred to the natural conditions.
RESULTS: Callus induction was better evidenced on Murashige and Skoog media containing 5 mg/L 2,4-dichlorophenoxyacetic acid up to fourth subculture. Callus differentiated into shoots on Murashige and Skoog media fortified with 6-benzylaminopurine or kinetin, whereas thidiazuron completely failed to regenerate shoots. Furthermore, microshoots rooted on 1.0 mg/L indole-3-butyric acid containing Murashige and Skoog media. The rooted plantlets were successfully acclimatized and established in soil with 88.3% survivability.
CONCLUSION: The type of auxins played an important role in inducing callus tissue from shoot bud explants of Safed musli. In future, this in vitro protocol could benefit in crop improvement programs and serve as a new source of bioactive compounds from Safed musli callus tissue for various therapeutic applications.
SUMMARY: Explants de-differentiated to form callus on Murashige and Skoog media containing 5 mg/L 2,4-D up to fourth subculture.Callus re-differentiated into shoots on Murashige and Skoog media fortified with 0.5 mg/L BAP.In vitro rooting of shoots was achieved on 1.0 mg/L IBA containing Murashige and Skoog media.The rooted plantlets were successfully acclimatized and established in soil with 88.3% survivability. Abbreviations used: MS: Murashige and Skoog, NAA: naphthalene acetic acid, 2,4-D: 2,4-dichlorophenoxyacetic acid, IAA: indole-3-acetic acid, BAP: 6-benzylaminopurine, Kn: Kinetin, TDZ: thidiazuron, IBA: indole-3-butyric acid, RCBD: Randomized Complete Block Design, DMRT: Duncan's Multiple Range Test.

Matched MeSH terms: Purines
Treatment of Lesch-Nyhan disease with S-adenosylmethionine: experience with five young Malaysians, including a girl

Chen BC, Balasubramaniam S, McGown IN, O'Neill JP, Chng GS, Keng WT, et al.

Brain Dev, 2014 Aug;36(7):593-600.
PMID: 24055166 DOI: 10.1016/j.braindev.2013.08.013

BACKGROUND: Lesch-Nyhan disease (LND) is a rare X-linked recessive neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8) which is responsible for recycling purine bases into purine nucleotides. Affected individuals have hyperuricemia leading to gout and urolithiasis, accompanied by a characteristic severe neurobehavioural phenotype with compulsive self-mutilation, extrapyramidal motor disturbances and cognitive impairment.
AIM: For its theoretical therapeutic potential to replenish the brain purine nucleotide pool, oral supplementation with S-adenosylmethionine (SAMe) was trialed in 5 Malaysian children with LND, comprising 4 related Malay children from 2 families, including an LND girl, and a Chinese Malaysian boy.
RESULTS: Dramatic reductions of self-injury and aggressive behaviour, as well as a milder reduction of dystonia, were observed in all 5 patients. Other LND neurological symptoms did not improve during SAMe therapy.
DISCUSSION: Molecular mechanisms proposed for LND neuropathology include GTP depletion in the brain leading to impaired dopamine synthesis, dysfunction of G-protein-mediated signal transduction, and defective developmental programming of dopamine neurons. The improvement of our LND patients on SAMe, particularly the hallmark self-injurious behaviour, echoed clinical progress reported with another purine nucleotide depletion disorder, Arts Syndrome, but contrasted lack of benefit with the purine disorder adenylosuccinate lyase deficiency. This first report of a trial of SAMe therapy in LND children showed remarkably encouraging results that warrant larger studies.
KEYWORDS: Aggression; Dystonia; HGPRT; HPRT1; Lesch–Nyhan disease; S-adenosylmethionine; Self-injury

Matched MeSH terms: Purines/metabolism

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