Famous Drug Research Articles

A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy

As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice.

Tailoring raloxifene into single-component molecular crystals possessing multilevel stimuli-responsive room-temperature phosphorescence

Simultaneously achieving room-temperature phosphorescence (RTP) and multiple-stimuli responsiveness in a single-component system is of significance but remains challenging. Crystallization has been recognized to be a workable strategy to fulfill the above task. However, how the molecular packing mode affects the intersystem crossing and RTP lifetime concurrently remains unclear so far. Herein, four economic small-molecular compounds, analogues of the famous drug raloxifene (RALO), are facilely synthesized and further explored as neat single-component and stimuli-responsive RTP emitters via crystallization engineering. Thanks to their simple structures and high ease to crystallize, these raloxifene analogues function as models to clarify the important role of molecular packing in the RTP and stimuli-responsiveness properties. Thorough combination of the single-crystal structure analysis and theoretical calculations clearly manifests that the tight antiparallel molecular packing mode is the key point to their RTP behaviors. Interestingly, harnessing the controllable and reversible phase transitions of the two polymorphs of RALO-OAc driven by mechanical force, solvent vapor, and heat, a single-component multilevel stimuli-responsive platform with tunable emission color is established and further exploited for optical information encryption. This work would shed light on the rational design of multi-stimuli responsive RTP systems based on single-component organics.

Taccalonolides: Structure, semi-synthesis, and biological activity.

Microtubules are the fundamental part of the cell cytoskeleton intimately involving in cell proliferation and are superb targets in clinical cancer therapy today. Microtubule stabilizers have become one of the effectively main agents in the last decades for the treatment of diverse cancers. Taccalonolides, the highly oxygenated pentacyclic steroids isolated from the genus of Tacca, are considered a class of novel microtubule-stabilizing agents. Taccalonolides not only possess a similar microtubule-stabilizing activity as the famous drug paclitaxel but also reverse the multi-drug resistance of paclitaxel and epothilone in cellular and animal models. Taccalonolides have captured numerous attention in the field of medicinal chemistry due to their variety of structures, unique mechanism of action, and low toxicity. This review focuses on the structural diversity, semi-synthesis, modification, and pharmacological activities of taccalonolides, providing bright thoughts for the discovery of microtubule-stabilizing drugs.

De novo biosynthesis and whole-cell catalytic production of paracetamol on a gram scale in Escherichia coli

We constructed the de novo biosynthesis and whole-cell biocatalysis pathways for the famous drug paracetamol or its analogues. This study provides a promising, sustainable, efficient alternative to the traditional chemical manufacturing methods.

Effect of metformin on Bax expression in pancreas and testis of normoglycemic albino rat: An immunohistochemical study

Metformin is a famous drug used to reduce blood glucose level. It could be used in treatment of polycystic ovarian syndrome. Metformin also demonstrated an anticancer activity. Bax, is one of the cellular apoptotic markers. Metformin was documented to increase the level of Bax protein. Based on the known facts about metformin and its new role as a potential inducer of cellular apoptosis, the current study has been designed to investigate the probable effects of the in-vivo metformin administration on the pancreatic and testicular tissues in normoglycemic rats, and its probable effect on Bax expression as one of the markers of cellular apoptosis Twenty rats divided in two groups; control and treated. Metformin treated rats were given 400mg/kg /day through oro-gastric tube for one month. After one month, rats in all groups were sacrificed, the pancreas and testis were dissected outto prepare paraffin sections, stained by hematoxylin&eosin, Masson’s trichrome stains and Bax immunohistochemical stain. Metformin treated group showed reduced pancreatic islets’ size with degenerated cells in both endocrine and exocrine parts, more fibers surrounding pancreatic acini, islets and blood vessels. Bax immunostaining showed intense reaction especially in the islets of Langerhans. The seminiferous tubules (STs) of the testis were irregular with disturbed degenerated spermatogenic cells. Extensive fibers surrounding seminiferous tubules and in the wall of the blood vessels were detected. Bax immunostaining showed intense reaction in the testis germinal cells of the treated group.: Our study revealed that metformin induced expression of Bax in pancreatic and testicular tissues of normal rats when used for one month, which will affect their viability and function. Its effect on Bax expression might be promising as a possible treatment in case of cancer, however, it should be used with caution.

The Impact of the Merge of Pfizer and Mylan Pharmaceuticals

First, in this deconstruction essay paper, the goal is to examine the acquisition and merger M&A of Pfizer Inc. (PFE) and Mylan, N.V. organizational relationships. Pfizer a famous global drug company known for their developing of product cures for erectile dysfunctions called ‘Viagra' as well as, globally recognized for the magic ‘blue pill' is one of the world's larger pharmaceutical firms in the world. Also, to focus on the economic model that will drive both Pfizer and Mylan's growth and investment in the organization's operations (internal growth). Next, the impact that this merger will have on the organization's size (external growth) that will be taken into consideration. Moreover, to deconstruct Mylan N.V. (MYL) global pharmaceutical company, specializing in the healthcare industry are they committed to raising the bar in manufacturing of high-quality medicine and will the combined forces of these two companies make a difference in the world of healthcare. Next, after they combine their products giving them a stronger pipeline to the public and private sector of the global healthcare industry will they survive?

Molecular encapsulation of Valganciclovir by β-cyclodextrin influences its binding to bovine serum albumin: a spectroscopic study

ABSTRACTWe report, in this paper, the stoichiometry, the binding constant and the structure of the β-cyclodextrin complex of the famous drug Valganciclovir. We investigate the influence of the complex formation of Valganciclovir with β-cyclodextrin, in the binding strength of the drug to the model carrier protein bovine serum albumin. Based on the electronic absorption, fluorescence and 2D rotating-frame Overhauser effect spectroscopy (ROESY) NMR spectral data, it follows that Valganciclovir forms a 1:1 complex with β-cyclodextrin. The β-CD molecule encapsulates the aliphatic chain of the substituted ester molecule. The association constant value of the drug-protein binding in the presence of β-cyclodextrin decreases from that in the absence of β-cyclodextrin, i.e., from that in the case of free drug, i.e. from 3.99 × 104 M−1 to 5.21 × 103 M−1. We compare the results of the binding of the drug to bovine serum albumin in free- and β-cyclodextrin-complex forms.

Investigating The Inhibition Of 5-LO Enzyme By Main Cannabinoids Contained In Cannabis Sativa And Seized Resin Cannabis By Using Molecular Modeling

Therapeutic cannabis is a subject which many researchers are very interested in all over the world. The effect of main compound of Cannabis is investigated to treat many diseases. Arachidonate 5-lypoxygenase (5-LO) is implicated in cancer progression, inflammation, tissue damage and other sickness. Commonly to inhibit 5-LO enzyme a famous drug Zileuton is used. In our work we compare inhibition of 5-LO by main compounds of cannabis using tools such as molecular mechanics, molecular dynamics and molecular docking by using MOE software (Molecular Operating Environment) [1]. Obtained results show that main cannabinoids inhibit 5- LO better than Zileuton.

Quantitative determination of five metabolites of aspirin by UHPLC–MS/MS coupled with enzymatic reaction and its application to evaluate the effects of aspirin dosage on the metabolic profile

Acetylsalicylic acid (Aspirin, ASA) is a famous drug for cardiovascular diseases in recent years. Effects of ASA dosage on the metabolic profile have not been fully understood. The purpose of our study is to establish a rapid and reliable method to quantify ASA metabolites in biological matrices, especially for glucuronide metabolites whose standards are not commercially available. Then we applied this method to evaluate the effects of ASA dosage on the metabolic and excretion profile of ASA metabolites in rat urine. Salicylic acid (SA), gentisic acid (GA) and salicyluric acid (SUA) were determined directly by UHPLC–MS/MS, while salicyl phenolic glucuronide (SAPG) and salicyluric acid phenolic glucuronide (SUAPG) were quantified indirectly by measuring the released SA and SUA from SAPG and SUAPG after β-glucuronidase digestion. SUA and SUAPG were the major metabolites of ASA in rat urine 24h after ASA administration, which accounted for 50% (SUA) and 26% (SUAPG). When ASA dosage was increased, the contributions dropped to 32% and 18%, respectively. The excretion of other three metabolites (GA, SA and SAPG) however showed remarkable increases by 16%, 6% and 4%, respectively. In addition, SUA and SUAPG were mainly excreted in the time period of 12–24h, while GA was excreted in the earlier time periods (0–4h and 4–8h). SA was mainly excreted in the time period of 0–4h and 12–24h. And the excretion of SAPG was equally distributed in the four time periods. We went further to show that the excretion of five metabolites in rat urine was delayed when ASA dosage was increased. In conclusion, we have developed a rapid and sensitive method to determine the five ASA metabolites (SA, GA, SUA, SAPG and SUAPG) in rat urine. We showed that ASA dosage could significantly influence the metabolic and excretion profile of ASA metabolites in rat urine.

The Hidden History of a Famous Drug: Tracing the Medical and Public Acculturation of Peruvian Bark in Early Modern Western Europe (c. 1650-1720).

The history of the introduction of exotic therapeutic drugs in early modern Europe is usually rife with legend and obscurity and Peruvian bark is a case in point. The famous antimalarial drug entered the European medical market around 1640, yet it took decades before the bark was firmly established in pharmaceutical practice. This article argues that the history of Peruvian bark can only be understood as the interplay of its trajectories in science, commerce, and society. Modern research has mostly focused on the first of these, largely due to the abundance of medico-historical data. While appreciating these findings, this article proposes to integrate the medical trajectory in a richer narrative, by drawing particular attention to the acculturation of the bark in commerce and society. Although the evidence we have for these two trajectories is still sketchy and disproportionate, it can nevertheless help us to make sense of sources that have not yet been an obvious focus of research. Starting from an apparently isolated occurrence of the drug in a letter, this article focuses on Paris as the location where medical and public appreciation of the bark took shape, by exploring several contexts of knowledge circulation and medical practice there. These contexts provide a new window on the early circulation of knowledge of the bark, at a time when its eventual acceptance was by no means certain.

Wavelength dispersive X-ray fluorescence analysis using fundamental parameter approach of Catha edulis and other related plant samples

This work is the first attempt to quantify trace elements in the Catha edulis plant (Khat) with a fundamental parameter approach. C. edulis is a famous drug plant in east Africa and Arabian Peninsula. We have previously confirmed that hydroxyapatite represents one of the main inorganic compounds in the leaves and stalks of C. edulis. Comparable plant leaves from basil, mint and green tea were included in the present investigation as well as trifolium leaves were included as a non-related plant. The elemental analyses of the plants were done by Wavelength Dispersive X-Ray Fluorescence (WDXRF) spectroscopy. Standard-less quantitative WDXRF analysis was carried out based on the fundamental parameter approaches. According to the standard-less analysis algorithms, there is an essential need for an accurate determination of the amount of organic material in the sample. A new approach, based on the differential thermal analysis, was successfully used for the organic material determination. The obtained results based on this approach were in a good agreement with the commonly used methods. Depending on the developed method, quantitative analysis results of eighteen elements including; Al, Br, Ca, Cl, Cu, Fe, K, Na, Ni, Mg, Mn, P, Rb, S, Si, Sr, Ti and Zn were obtained for each plant. The results of the certified reference materials of green tea (NCSZC73014, China National Analysis Center for Iron and Steel, Beijing, China) confirmed the validity of the proposed method.

Molecular Modeling Study of Drug-DNA Combined to Single Walled Carbon Nanotube

One of the applications of nanotechnology is use of carbon nanotubes for the targeted delivery of drug molecules. To demonstrate the physical and chemical properties of biomolecules and identify new material of drug properties, the interaction of carbon nanotubes (CNTs) with biomolecules is a subject of many investigations. CNTs is a synthetic compound with extraordinary mechanical, thermal, electrical, optical, and chemical properties widely applied for technological purposes. In this article we have tried to investigate thermodynamic parameters and dielectric effects in different solvents for one of the most famous anticancer drug “cisplatin” combined to SWCNT, by Monte Carlo and density functional theory (DFT) calculations. Cause of platinum element in cisplatin we have done calculations as Gibbs free energy, thermal enthalpy, thermal energy and entropy at 6-31G** basis set with SCRF model of solvent. In this work, the major point has been embedded that results of both two methods of Monte Carlo and DFT can overlap with each other and cisplatin- SWCNT is a suitable compound for drug delivery in different media.

Trouble with translational medicine and bad news for mice

Defining translational medicine is not easy, but Marincola rightly pointed out that it is in trouble [1]. This paradigm cannot mask the continuous decline in the output of efficient therapies and the incredible rise in investments for research. For example, amongst 97 new drugs or new indications that were granted an authorization in France in 2010, la revue Prescrire, the famous independent drug bulletin, onlyrated4asprovidinga therapeuticadvantage [2].

ChemInform Abstract: Quinolines and Structurally Related Heterocycles as Antimalarials

AbstractReview: 152 refs.

Process standardization of Rasamanikya

Rasamanikya is a famous drug, frequently used by Ayurvedic physicians for Vata-Kaphaja diseases like Shwasa, Kasa and Kushtha (Skin disorders). Various methods of preparation have been found described in Rasa classics. Generally it is prepared by Shuddha Haratala which is kept between two thin transparent Abharaka Patra (mica sheets) in small scale and in sharava for large scale, heated up to desired level. There are so many methods and different liquid media have been found described for Shodhana of Haratala. Therefore the methods of preparation of Rasamanikya and Shodhana process of Haratala have been validated through various experiments. Tankana-treated Haratala (T. Treated) is found best for Shodhana process and final product too i.e. Rasamanikya in terms of pharmaceutical standards i.e. Ruby in colour, along with reproducibility of fixed quality.

Biotechnological Potential of Marine Sponges and their Associated Bacteria as Producers of New Pharmaceuticals (Part II)

AbstractThe supply problemThe examples of sponge-derived compounds in advanced stages of clinical trials presented in part I of this article emphasize the potential of sponges as auspicious source for drugs against various human diseases.However, compared to the vast number of over 4000 compounds isolated from sponges during the last three decades, the number of sponge-derived drugs that have already entered the market is surprisingly small. There are two major reasons for this phenomenon: One is the extremely long time frame involved in the process of drug development. For instance, to develop the famous anticancer drug Taxol® from its initial description in the yew tree to its approval as a commercial pharmaceutical took over 20 years. The presented examples of sponge-derived compounds in clinical trials, this long time frame is by far no exception. Thus, as many interesting compounds were initially reported already in the 1980s and early 1990s, there is hope that within the following years the number of commercially available ”marine drugs” will considerably increase.

A CHINESE BASE FOR DRUG RESEARCH

THE PAST THREE YEARS HAVE been a dizzying ride for Ge Li, the founder of Shanghai-based WuXi PharmaTech. Li, 37, started the contract research company in 2001 when he returned home to China after 12 years of living in the U.S. He tripled his sales in the 2002-03 fiscal year and expects sales to double again this year. Within a year or two, Li will be employing 500 scientists. U.S. competitors that had earlier expressed doubts about PharmaTech's capabilities are now trying to cooperate with the firm, he says. PharmaTech's rented labs in Shanghai's Waigaoqiao Free Trade Zone are like an R&D mall of the world's most famous drug companies. One room handles projects for Sumitomo Chemical, another room takes care of Merck & Co. projects, and scientists in the next room work for another major pharma company. In one conference hall, a researcher from Eli Lilly is giving a ...

Book Review

Dr E. F. Steinmetz: Piper methysticum (Kava), famous drug plant of the South Sea islands. Illustrated. 46 pp., 21 figs., paper bound, $ 2,20. Published by the author, 347 Keizersgracht, Amsterdam.