Targeting antioxidant pathways with ferrocenylated N-heterocyclic carbene supported gold(I) complexes in A549 lung cancer cells

Arambula, J. F.,McCall, R.,Sidoran, K. J.,Magda, D.,Mitchell, N. A.,Bielawski, C. W.,Lynch, V. M.,Sessler, J. L.,Arumugam, K. THE ROYAL SOCIETY OF CHEMISTRY 2016 Chemical Science Vol.7 No.2

<P>Ferrocene containing N-heterocyclic carbene (NHC) ligated gold(I) complexes of the type [Au(NHC)(2)](+) were prepared and found to be capable of regulating the formation of reactive oxygen species (ROS) via multiple mechanisms. Single crystal X-ray analysis of bis(1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene)-gold(I) chloride (5) and bis(1,3-di(ferrocenylmethyl)imidazol-2-ylidene)-gold(I) chloride (6) revealed a quasi-linear geometry around the gold(I) centers (i.e., the C-Au-C bond angle were measured to be similar to 177 degrees and all the Au-C-carbene bonds distances were in the range of 2.00 (7)-2.03 (1) angstrom). A series of cell studies indicated that cell proliferation inhibition and ROS generation were directly proportional to the amount of ferrocene contained within the [Au(NHC)(2)](+) complexes (IC50 of 6 < 5 < bis(1-benzyl-3-mesitylimidazol-2-ylidene)-gold(I) chloride (4)). Complexes 4-6 were also confirmed to inhibit thioredoxin reductase as inferred from lipoate reduction assays and increased chelatable intracellular zinc concentrations. RNA microarray gene expression assays revealed that 6 induces endoplasmic reticulum stress response pathways as a result of ROS increase.</P>

Subunit Principle: Key Element for Plantar Reconstruction with Free Sensate Flaps

Blanca Yadira Arambula Sanchez,Daniel De Luna Gallardo,Jaime Aron Garcia-Espinoza,David Flores Soto 대한수부외과학회 2021 대한수부외과학회지 Vol.26 No.1

Purpose: Plantar wounds represent a frequent practice of the plastic and reconstructive surgeon. The uniqueness and high complexity of the microarchitecture and biomechanics of the plantar region explain the complex challenge of its reconstruction. With the advances in microsurgery, including the plantar subunit principle, both applied in the restoration of plantar defects through the use of sensorineural free flaps have allowed an optimal reconstruction. Methods: A descriptive, retrospective study was carried out in a period of time established between January 2016 and January 2019, obtaining a total of 18 patients with plantar defects, reconstructed using sensory free flaps. Tissue stability, recovery of protective sensitivity, early ambulation, and correct use of footwear were evaluated. Results: The most frequent etiology was secondary to oncological resections due to melanoma (n = 12, 66.7%), followed by gunshot wounds (n = 4, 22.2%). Subunit 3 was the most frequently involved in 38.9% (n = 7). In the 88.8% of the cases, was used an anterolateral thigh flap (n = 16) and the lateral antebrachial flap in 22.2% (n = 2). The free flap survival rate was 100%. An average of seven points was obtained at 6 months based on the Semmes-Weinstein test. The mean for the return to their daily activities was 2.5 months. The patients of 94.4% (n = 17) recovered ambulation and could footwear. Conclusion: The reconstruction of plantar defects must have a systematic approached, taking the subunit principle as a central point. The treatment of plantar defects with sensorineural free flaps represent an unprecedented option for optimal reconstruction.

Recent Developments in Texaphyrin Chemistry and Drug Discovery

Preihs, Christian,Arambula, Jonathan F.,Magda, Darren,Jeong, Heeyeong,Yoo, Dongwon,Cheon, Jinwoo,Siddik, Zahid H.,Sessler, Jonathan L. American Chemical Society 2013 Inorganic chemistry Vol.52 No.21

<P>Texaphyrins are pentaaza expanded porphyrins with the ability to form stable complexes with a variety of metal cations, particularly those of the lanthanide series. In biological milieus, texaphyrins act as redox mediators and mediate the production of reactive oxygen species (ROS). In this review, newer studies involving texaphyrin complexes targeting several different applications in anticancer therapy are described. In particular, the preparation of bismuth and lead texaphyrin complexes as potential α-core emitters for radiotherapy is detailed, as are gadolinium texaphyrin functionalized magnetic nanoparticles with features that make them of interest as dual-mode magnetic resonance imaging contrast agents and as constructs with anticancer activity mediated through ROS-induced sensitization and concurrent hyperthermia. Also discussed are gadolinium texaphyrin complexes as possible carrier systems for the targeted delivery of platinum payloads.</P><P>Texaphyrins are pentaaza expanded porphyrins with the ability to form stable complexes with a variety of metal cations, particularly those of the lanthanide series. In biological milieus, texaphyrins act as redox mediators and mediate the production of reactive oxygen species. In this review, newer studies involving texaphyrin complexes targeting several different applications in anticancer therapy are described.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/inocaj/2013/inocaj.2013.52.issue-21/ic400226g/production/images/medium/ic-2013-00226g_0016.gif'></P>

Bismuth– and lead–texaphyrin complexes: towards potential α-core emitters for radiotherapy

Preihs, Christian,Arambula, Jonathan F.,Lynch, Vincent M.,Siddik, Zahid H.,Sessler, Jonathan L. The Royal Society of Chemistry 2010 Chemical communications Vol.46 No.42

<P>Lead(<SMALL>II</SMALL>)–texaphyrins and the first discrete binuclear μ–oxo bismuth(<SMALL>III</SMALL>)–texaphyrin are reported. The latter was characterized <I>via</I>single crystal X-ray diffraction analysis. Cell proliferation assays using the A2780 ovarian cancer cell line were used to determine the cytotoxicity of the complexes.</P> <P>Graphic Abstract</P><P>Bismuth(<SMALL>III</SMALL>)– and lead(<SMALL>II</SMALL>)–texaphyrins have been synthesized with Bi(<SMALL>III</SMALL>) residing in a unique binuclear μ–oxo coordination sphere. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0cc03528a'> </P>

Targeting Heterogeneous Tumors Using a Multifunctional Molecular Prodrug

Sharma, Amit,Lee, Min-Goo,Won, Miae,Koo, Seyoung,Arambula, Jonathan F.,Sessler, Jonathan L.,Chi, Sung-Gil,Kim, Jong Seung American Chemical Society 2019 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.141 No.39

<P>Reported here is a molecular construct (<B>K1</B>) designed to overcome hurdles associated with delivering active drugs to heterogeneous tumor environments. Construct <B>K1</B> relies on two cancer environment triggers (GSH and H<SUB>2</SUB>O<SUB>2</SUB>) to induce prodrug activation. It releases an active drug form (SN-38) under conditions of both oxidative and reductive stress <I>in vitro</I>. Specific uptake of <B>K1</B> in COX-2 positive aggressive colon cancer cells (SW620 and LoVo) was seen, along with enhanced anticancer activity compared with the control agent SN-38. These findings are attributed to environmentally triggered drug release, as well as simultaneous scavenging of species giving rise to intracellular redox stress. <B>K1</B> serves to downregulate various cancer survival signaling pathways (AKT, p38, IL-6, VEGF, and TNF-α) and upregulate an anti-inflammatory response (IL-10). Compared with SN-38 and DMSO as controls, <B>K1</B> also displayed an improved <I>in vivo</I> therapeutic efficacy in a xenograft tumor regrowth model with no noticeable systematic toxicity at the administrated dose. We believe that the strategy described here presents an attractive approach to addressing solid tumors characterized by intratumoral heterogeneity.</P> [FIG OMISSION]</BR>

A Pyrrolyl-Based Triazolophane: A Macrocyclic Receptor With CH and NH Donor Groups That Exhibits a Preference for Pyrophosphate Anions

Sessler, Jonathan L.,Cai, Jiajia,Gong, Han-Yuan,Yang, Xiaoping,Arambula, Jonathan F.,Hay, Benjamin P. American Chemical Society 2010 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.132 No.40

<P>A pyrrolyl-based triazolophane, incorporating CH and NH donor groups, acts as a receptor for the pyrophosphate anion in chloroform solution. It shows selectivity for this trianion, followed by HSO<SUB>4</SUB><SUP>−</SUP> > H<SUB>2</SUB>PO<SUB>4</SUB><SUP>−</SUP> > Cl<SUP>−</SUP> > Br<SUP>−</SUP> (all as the corresponding tetrabutylammonium salts), with NH−anion interactions being more important than CH−anion interactions. In the solid state, the receptor binds the pyrophosphate anion in a clip-like slot <I>via</I> NH and CH hydrogen bonds.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2010/jacsat.2010.132.issue-40/ja107098r/production/images/medium/ja-2010-07098r_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja107098r'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja107098r'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja107098r'>ACS Electronic Supporting Info</A></P>

Relief of Night-time Symptoms Associated With Gastroesophageal Reflux Disease Following 4 Weeks of Treatment With Pantoprazole Magnesium; The Mexican Gastroesophageal Reflux Disease Working Group

( Juan Carlos Lopez Alvarenga ),( William Orr ),( Jose Antonio Vargas Romero ),( Jose Maria Remes Troche ),( Miguel Morales Arambula ),( Julio Cesar Soto Perez ),( Gualberto Mateos Perez ),( Sergio So 대한소화기기능성질환·운동학회 2014 Journal of Neurogastroenterology and Motility (JNM Vol.20 No.1

Background/Aims To evaluate the effectiveness of pantoprazole magnesium (pantoprazole-Mg) 40 mg in the relief of esophageal and extra- esophageal symptoms of gastroesophageal reflux disease (GERD), particularly night-time symptoms. Methods Patients (aged 18-50 years) with 3-month history of heartburn and/or acid regurgitation plus at least one other symptom in the last week were enrolled in a nationwide, prospective and observational study in Mexico. Patients received pantoprazole-Mg 40 mg once daily during 4 weeks. Symptoms were assessed through a physician-administered structured interview and the patient- completed ReQuest in PracticeTM questionnaire. Night-time GERD was defined as arousal from sleep during the night due to GERD-associated symptoms. Results Out of 4,343 patients included at basal visit, 3,665 were considered for the effectiveness per protocol analysis. At baseline, patients had a median of 8 GERD related symptoms. Patients with night-time GERD symptoms (42.7%) were more likely to have extra-esophageal symptoms (P < 0.001) than other GERD patients. Pantoprazole-Mg 40 mg once daily for 4 weeks improved a broad range of GERD-associated symptoms from baseline (80% reduction on physicians assessments; 68-77% reduction on ReQuest in PracticeTM dimensions), including both day- and night-time GERD symptoms; improvements were the greatest for extra-esophageal symptoms in patients with night-time symptoms. Pantoprazole-Mg was well tolerated. Conclusions Pantoprazole-Mg 40 mg significantly improved a broad range of esophageal and extra-esophageal GERD related symptoms including sleep disturbances, as well as well-being, in patients with daytime or night-time GERD, making it a good option for patients with GERD, especially when extra-esophageal and night-time symptoms are present. (J Neurogastroenterol Motil 2014;20:64-73)