Publications
The Healing Power Of Dietary Supplements To Prevent Long-Term Covid-19; A Prospective Observation Study
Apr 18, 2024Journal Polytechnic Journal
Publisher Polytechnical University/Erbile
DOI https://doi.org/10.59341/2707-7799.1804
Issue 1
Volume 14
The novel coronavirus which emerged from Wuhan, China, in December 2019, was first described as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affects different systems in the body resulting in different symptoms and severity. The role of macro and micro nutrients plus gut microbiome (gut-lung axis) to boost the immune system is well documented. Therefore, this study aims to boost the immune system particularly the lung immunity to shorten the infection course and prevent post-covid complications. The study strategy depends on maintaining the maximum nutritional status for wellfunctioning immune system, directing immune system to focus on viral infection by minimizing all the other oxidative stress pathways that cause further damage and put the body immune system under pressure. Furthermore, this study exploits all the possible mechanisms that could promote lung immunity via boosting healthy microbiome. This study includes 183 patients with positive PCR test and typical COVID-19 symptoms from Feb 2020 to Jun 2022. The patients were guided to follow a designed protocol which includes food supplements and healthy diet and nutrition. After 3 days of the protocol initiation, the covid score reduced by 1.14 (p
A ferrocene-containing nucleoside analogue targets DNA replication in pancreatic cancer cells
Jun 11, 2022Journal Metallomics
Publisher Royal Society of Chemistry
DOI https://doi.org/10.1093/mtomcs/mfac041.
Issue 14
Volume 7
Pancreatic ductal adenocarcinoma ( PDAC ) is a disease that remains refractory to existing treatments including the nucleoside ana- logue gemcitabine. In the current study we demonstrate that an organometallic nucleoside analogue, the ferronucleoside 1- ( S ,R p ) , is cytotoxic in a panel of PDAC cell lines including gemcitabine-resistant MIAPaCa2, with IC 50 values comparable to cisplatin. Biochemical studies show that the mechanism of action is inhibition of DNA replication, S-phase cell cycle arrest and stalling of DNA-replication forks, which were directly observed at single molecule resolution by DNA-fibre fluorography. In agreement with this, transcriptional changes following treatment with 1- ( S ,R p ) include activation of three of the four genes ( HUS1 , RAD1 , RAD17 ) of the 9-1-1 check point complex clamp and two of the three genes ( MRE11 , NBN ) that form the MRN complex as well as activation of multiple downstream targets. Furthermore, there was evidence of phosphorylation of checkpoint kinases 1 and 2 as well as RPA1 and gamma H2AX, all of which are considered biochemical markers of replication stress. Studies in p53-deficient cell lines showed activation of CDKN1A ( p21 ) and GADD45A by 1- ( S ,R p ) was at least partially independent of p53. In conclusion, because of its potency and activity in gemcitabine- resistant cells, 1- ( S ,R p ) is a promising candidate molecule for development of new treatments for PDAC.
Effect of regiochemistry and methylation on the anticancer activity of a ferrocene-containing organometallic nucleoside analogue
Sep 1, 2020Journal Chem. Bio. Chem.
Publisher WILEY-V C H VERLAG GMBH
DOI https://doi.org/10.1002/cbic.202000124
Issue 17
Volume 21
Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group, and either a thyminyl or methylthyminyl group, have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,Rp), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1- (S,Rp), which only differs from the lead compound by being substituted on two cyclopentadienyl rings rather than one, was over twenty times less cytotoxic. On the other hand methylated derivatives of 1-(S,Rp) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,Rp) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.
Organometallic nucleoside analogues: effect of the metallocene metal atom on cancer cell line toxicity
Dec 9, 2019Journal Dalton Transactions
Publisher Royal Society of Chemistry
DOI 10.1039/c9dt04174e
Issue 49
Volume 2020
A new chiral organometallic nucleoside analogue containing ruthenocene is reported, in which alkylthymine and alkylhydroxyl groups are attached in adjacent positions on one cyclopentadienyl ring. The synthetic procedures for this metallocene derivative and two control compounds are described, along with their characterisation by cyclic voltammetry and X-ray crystallography. Their biological activities in a human pancreatic cancer cell line (MIA-Pa-Ca-2) were significantly lower than those of three previously reported analogous ferrocene compounds, indicating that the choice of metallocene metal atom (Fe or Ru) plays a pivotal role in determining the anticancer properties of these nucleoside analogues, which in turn suggests a different mode of action from that of a conventional nucleoside analogue.
Organometallic Nucleoside Analogues: Effect of Hydroxyalkyl Linker Length on Cancer Cell Line Toxicity
Oct 17, 2016Journal Eur. J. Inorg. Chem
Publisher WILEY-V C H VERLAG GMBH
DOI https://doi.org/10.1002/ejic.201600853
Issue 2
Volume 2017
A new series of chiral ferrocene derivatives containing both a hydroxyalkyl group and a thyminyl group on one cyclopentadienyl ring have been synthesised to probe structure– activity relationships in cancer cell line cytotoxicities. The stereoisomers of enantiomeric pairs of these so-called ferronucleosides have been studied and characterised by a combination of chiral analytical HPLC and single-crystal X-ray diffraction. Biological activity studies revealed that changing the length of the hydroxyalkyl group had marked effects on IC50 values, with compounds having shorter arms that more closely resemble endogenous nucleosides exhibiting lower cytotoxicities. The lipophilicities and electrochemical properties of this compound series have been studied to rationalise these trends and indicate future directions of study.