Development of Metal-Based Drugs and Application in Clinical Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Ming Shao ◽  
Bold Sharavyn ◽  
Ping Huang ◽  
Hua Naranmandura ◽  
Qian Qian Wang

Abstract: Metals occur naturally in soil and many kinds of rocks, particularly in minerals and ores, which also play a vital role in living systems such as plants and animals. Over a long period of time , metal evolution from toxin to the drug has achieved a milestone in medicine. Currently, a few metal-based drugs (i.e., metallodrugs) have been used in the clinic to treat patients with different medical conditions, making exciting new developments in anticancer therapeutics (e.g., arsenic trioxide and cisplatin) that quickly move into focus. Moreover, a thorough understanding of the properties and effects of metals on the human body could improve the development and innovation of metal-based drugs. In this review, we have comprehensively described the discovery and development of metal-based anticancer drugs, as well as their side effects in clinical treatment. Although metallodrugs have shown promising outcomes in the treatment of cancers, further investigation is needed to optimize their side effect for broader applications.

2020 ◽  
Vol 16 (11) ◽  
pp. 843-848
Author(s):  
Manikkam Rajalakshmi ◽  

Identification of the toxicity of compounds is more crucial before entering clinical trials. Awareness of physiochemical properties, possible targets and side effects has become a major public health issue to reduce risks. Experimental determination of analyzing the physiochemical properties of a drug, their interaction with specific receptors and identifying their side-effects remain challenging is time consuming and costly. We describe a manually compiled database named DaiCee database, which contains 2100 anticancer drugs with information on their physiochemical properties, targets of action and side effects. It includes both synthetic and herbal anti-cancer compounds. It allows the search for SMILES notation, Lipinski’s and ADME/T properties, targets and side effect profiles of the drugs. This helps to identify drugs with effective anticancer properties, their toxic nature, drug-likeness for in-vitro and in-vivo experiments. It also used for comparative analysis and screening of effective anticancer drugs using available data for compounds in the database. The database will be updated regularly to provide the users with latest information. The database is available at the URL http://www.hccbif.org/usersearch.php


Phlebologie ◽  
2004 ◽  
Vol 33 (06) ◽  
pp. 202-205 ◽  
Author(s):  
K. Hartmann ◽  
S. Nagel ◽  
T. Erichsen ◽  
E. Rabe ◽  
K. H. Grips ◽  
...  

SummaryHydroxyurea (HU) is usually a well tolerated antineoplastic agent and is commonly used in the treatment of chronic myeloproliferative diseases. Dermatological side effects are frequently seen in patients receiving longterm HU therapy. Cutaneous ulcers have been reported occasionally.We report on four patients with cutaneous ulcers whilst on long-term hydroxyurea therapy for myeloproliferative diseases. In all patients we were able to reduce the dose, or stop HU altogether and their ulcers markedly improved. Our observations suggest that cutaneous ulcers should be considered as possible side effect of long-term HU therapy and healing of the ulcers can be achieved not only by cessation of the HU treatment, but also by reducing the dose of hydroxyurea for a limited time.


2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.


2019 ◽  
Vol 19 (8) ◽  
pp. 1037-1047 ◽  
Author(s):  
Jihene Elloumi-Mseddi ◽  
Dhouha Msalbi ◽  
Raouia Fakhfakh ◽  
Sami Aifa

Background:Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates.Objective:In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).Methods:Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity.Results:Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect.Conclusion:Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mona Dietrichkeit ◽  
Marion Hagemann-Goebel ◽  
Yvonne Nestoriuc ◽  
Steffen Moritz ◽  
Lena Jelinek

AbstractAlthough awareness of side effects over the course of psychotherapy is growing, side effects are still not always reported. The purpose of the present study was to examine side effects in a randomized controlled trial comparing Metacognitive Training for Depression (D-MCT) and a cognitive remediation training in patients with depression. 84 patients were randomized to receive either D-MCT or cognitive remediation training (MyBrainTraining) for 8 weeks. Side effects were assessed after the completion of each intervention (post) using the Short Inventory of the Assessment of Negative Effects (SIAN) and again 6 months later (follow-up) using the Negative Effects Questionnaire (NEQ). D-MCT and MyBrainTraining did not differ significantly in the number of side effects. At post assessment, 50% of the D-MCT group and 59% of the MyBrainTraining group reported at least one side effect in the SIAN. The most frequently reported side effect was disappointment in subjective benefit of study treatment. At follow-up, 52% reported at least one side effect related to MyBrainTraining, while 34% reported at least one side effect related to the D-MCT in the NEQ. The most frequently reported side effects fell into the categories of “symptoms” and “quality”. Our NEQ version was missing one item due to a technical error. Also, allegiance effects should be considered. The sample size resulted in low statistical power. The relatively tolerable number of side effects suggests D-MCT and MyBrainTraining are safe and well-received treatment options for people with depression. Future studies should also measure negative effects to corroborate our results.


2018 ◽  
Vol 31 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Andrea Albrecht ◽  
Theresa Penger ◽  
Michaela Marx ◽  
Karin Hirsch ◽  
Helmuth G. Dörr

AbstractBackground:Despite the fact that priming with sex steroids in prepubertal children before growth hormone (GH) provocative tests is recommended, there is an ongoing controversial discussion about the appropriate age of the children, the drug used for priming, the dose and the period between priming and the GH test. Interestingly, there is no discussion on the safety of this procedure. To date, only little data have been available on the possible side effects of priming with testosterone.Methods:We analyzed the outcome in 188 short-statured prepubertal boys who had been primed with testosterone enanthate (n=136: 50 mg; n=51: 125 mg, and accidentally one boy with 250 mg) 7 days prior to the GH test. Serum testosterone levels were measured on the day of the GH test in 99 boys.Results:Overall, only five boys developed adverse side effects. Two boys (dose 125 mg) showed severe low-flow priapism and had to undergo decompression of the corpora cavernosa. One boy suffered from self-limiting priapism and testicular pain (dose 50 mg). Two patients reported testicular pain (each dose 50 mg). The single patient with 250 mg testosterone did not show any adverse effects. The total side effect rate was 2.7%. The serum testosterone levels of the boys with side effects were not different from the testosterone levels of the boys without any side effects.Conclusions:Parents and patients should be informed about the possible side effects of priming with testosterone such as priapism and testicular pain. However, the overall side effect rate is low. We found no correlation between the outcome and the testosterone dose used and/or the level of serum testosterone.


Author(s):  
Meysam T. Chorsi ◽  
Pouya Tavousi ◽  
Caitlyn Mundrane ◽  
Vitaliy Gorbatyuk ◽  
Kazem Kazerounian ◽  
...  

Abstract Natural nanomechanisms such as capillaries, neurotransmitters, and ion channels play a vital role in the living systems. But the design principles developed by nature through evolution are not well understood and, hence, not applicable to engineered nanomachines. Thus, the design of nanoscale mechanisms with prescribed functions remains a challenge. Here, we present a systematic approach based on established kinematics techniques to designing, analyzing, and controlling manufacturable nanomachines with prescribed mobility and function built from a finite but extendable number of available "molecular primitives." Our framework allows the systematic exploration of the design space of irreducibly simple nanomachines, built with prescribed motion specification by combining available nanocomponents into systems having constrained, and consequently controllable motions. We show that the proposed framework has allowed us to discover and verify a molecule in the form of a seven link, seven revolute (7R) close loop spatial linkage with mobility (degree of freedom) of one. Furthermore, our experiments exhibit the type and range of motion predicted by our simulations. Enhancing such a structure into functional nanomechanisms by exploiting and controlling their motions individually or as part of an ensemble could galvanize development of the multitude of engineering, scientific, medical, and consumer applications that can benefit from engineered nanomachines.


2021 ◽  
Vol 111 (4) ◽  
Author(s):  
James A. Wright ◽  
Jessica A. Wenz ◽  
Gabrielle Jackson Madrigal

Triamcinolone acetonide is a synthetic glucocorticoid used to treat numerous acute and chronic inflammatory conditions. The various side effects of this drug from parenteral administration are well documented in the literature. In this study, three patients present with a rare side effect of violaceous dermal pigmentation. To the best of the authors' knowledge, this finding is rarely presented in the current literature. The purpose of this study is to provide awareness of a less-documented, delayed side effect from triamcinolone acetonide administration. Although all patients presenting in this study had a known history of autoimmune disease (eg, lupus, psoriatic arthritis) further research is needed to suggest a possible association between dermal violaceous change and the use of triamcinolone.


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