In Drug Repurposing Tactics Against Covid-19

Background: Now a days, due to high substantial costs and slow rate of new drug discovery and development, repurposing of old drugs to treat diseases is becoming an emerging drug approach. Repurposing approach involves the identification of new pharmacological activity for old drugs. This strategy is time saving, more effective and has lesser failure risks. Methods: The present review involves the challenge by summarising the COVID‐19 drug repurposing research into three large groups, including repurposing of Antivirals, Anti-Cancer Drugs, existing Quinoline based drugs. Results: Number of medications, for example remdesivir, umifenovir, favipiravin, ribavirin, rapamycin, carfilzomib, chloroquine and hydroxychloroquine, saquinavir, elvitegravir, and oxolinic acid and rilapladib have indicated inhibitory effects against the SARS-CoV2 in vitro just as in clinical conditions. These medications either act through infection related targets, for example, RNA genome, polypeptide pressing and take-up pathways or target have related pathways including angiotensin-changing over protein 2 (ACE2) receptors also, inflammatory pathways. Conclusion: From the literature studies it can be concluded that, In the current scenario repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.

Download Full-text

Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis

10.21203/rs.3.rs-52126/v1 ◽

2020 ◽

Author(s):

Qiaoming Zhi ◽

Wei Li ◽

Dongming Zhu ◽

Daiwei Wan ◽

Ye Han ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Model ◽

Migration And Invasion ◽

Inhibitory Effects ◽

Biochemical Basis ◽

Over Expression ◽

Anti Cancer ◽

Ic50 Values ◽

Anti Tumor Activity

Abstract Background The polyether antibiotic nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of nigericin. In addition, the inhibitory effects of nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by nigericin. Meanwhile, the inhibitory effects of nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.

Download Full-text

In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates

Molecules ◽

10.3390/molecules24122255 ◽

2019 ◽

Vol 24 (12) ◽

pp. 2255 ◽

Cited By ~ 1

Author(s):

Abd El-Galil E. Amr ◽

Alhussein A. Ibrahimd ◽

Mohamed F. El-Shehry ◽

Hanaa M. Hosni ◽

Ahmed A. Fayed ◽

...

Keyword(s):

Chloroacetic Acid ◽

Aromatic Aldehydes ◽

Mercaptoacetic Acid ◽

Inhibitory Effects ◽

In Vivo Experiments ◽

Schiff Base Derivatives ◽

Anti Cancer ◽

Mcf 7

In this study, some of new thiophenyl thienopyrimidinone derivatives 2–15 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of 2 with ethyl- chloroacetate gave thienopyrimidinone N-ethylacetate 3, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide 4 and benzo[d][1,3]oxazin-4-one 5, respectively. Condensation of 4 with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives 6,7, and thiosemicarbazise 10, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones 8, 9, and phenylimino-thiazolidinone 11, respectively. Treatment of 4 with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole 12 and acetyl acetohydrazide 13 derivatives, respectively. The latter compound 13 was reacted with ethyl cycno-acetate or malononitrile to give 14 and 15, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8th day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.

Download Full-text

The Anticancer Effect of Sanguinarine: A Review

Current Pharmaceutical Design ◽

10.2174/1381612824666180829100601 ◽

2018 ◽

Vol 24 (24) ◽

pp. 2760-2764 ◽

Cited By ~ 7

Author(s):

Chenxing Fu ◽

Guiping Guan ◽

Hongbing Wang

Keyword(s):

Tumor Cell ◽

In Vivo Studies ◽

Inhibitory Effects ◽

Anticancer Effect ◽

Growth Inhibitory ◽

Cell Proliferation Inhibition ◽

Anti Cancer ◽

Induced Apoptosis

In vitro and in vivo studies have revealed that Sanguinarine has antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects on tumor cells of a variety of cancers. Previous research showed that sanguinarine induced apoptosis (cell death) and/or antiproliferative while reducing tumor cell antiangiogenic and anti-invasive properties. This paper describes various sanguinarine anti-cancer mechanisms, including inhibition of erroneously-activated signal transduction pathways, apoptosis, and tumor cell proliferation inhibition.

Download Full-text

Repurposing mesalazine against cardiac fibrosis in vitro

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-020-01998-9 ◽

2020 ◽

Author(s):

Maximilian Hoffmann ◽

Theresa A. Kant ◽

Ramona Emig ◽

Johanna S. E. Rausch ◽

Manja Newe ◽

...

Keyword(s):

Cardiac Fibrosis ◽

Drug Repurposing ◽

Fibroblast Cell ◽

Cardiac Fibroblast ◽

Cell Stiffness ◽

Fibroblast Proliferation ◽

Time Saving ◽

Solvent Control ◽

Vitro Model

Abstract Cardiovascular diseases are exacerbated and driven by cardiac fibrosis. TGFβ induces fibroblast activation and differentiation into myofibroblasts that secrete excessive extracellular matrix proteins leading to stiffening of the heart, concomitant cardiac dysfunction, and arrhythmias. However, effective pharmacotherapy for preventing or reversing cardiac fibrosis is presently unavailable. Therefore, drug repurposing could be a cost- and time-saving approach to discover antifibrotic interventions. The aim of this study was to investigate the antifibrotic potential of mesalazine in a cardiac fibroblast stress model. TGFβ was used to induce a profibrotic phenotype in a human cardiac fibroblast cell line. After induction, cells were treated with mesalazine or solvent control. Fibroblast proliferation, key fibrosis protein expression, extracellular collagen deposition, and mechanical properties were subsequently determined. In response to TGFβ treatment, fibroblasts underwent a profound phenoconversion towards myofibroblasts, determined by the expression of fibrillary αSMA. Mesalazine reduced differentiation nearly by half and diminished fibroblast proliferation by a third. Additionally, TGFβ led to increased cell stiffness and adhesion, which were reversed by mesalazine treatment. Collagen 1 expression and deposition—key drivers of fibrosis—were significantly increased upon TGFβ stimulation and reduced to control levels by mesalazine. SMAD2/3 and ERK1/2 phosphorylation, along with reduced nuclear NFκB translocation, were identified as potential modes of action. The current study provides experimental pre-clinical evidence for antifibrotic effects of mesalazine in an in vitro model of cardiac fibrosis. Furthermore, it sheds light on possible mechanisms of action and suggests further investigation in experimental and clinical settings.

Download Full-text

Inhibitory effects of (-)-Epigallocatechin-3-gallate from green tea on the growth of Babesia parasites

Parasitology ◽

10.1017/s0031182009991594 ◽

2009 ◽

Vol 137 (5) ◽

pp. 785-791 ◽

Cited By ~ 25

Author(s):

M. ABOULAILA ◽

N. YOKOYAMA ◽

I. IGARASHI

Keyword(s):

Body Weight ◽

Green Tea ◽

Inhibitory Effect ◽

Post Inoculation ◽

Chemotherapeutic Drug ◽

Inhibitory Effects ◽

Viability Test ◽

Anti Cancer

SUMMARY(-)-Epigallocatechin-3-gallate (EGCG) is the major tea catechin and accounts for 50–80% of the total catechin in green tea. (-)-Epigallocatechin-3-gallate has antioxidant, anti-inflammatory, anti-microbial, anti-cancer, and anti-trypanocidal activities. This report describes the inhibitory effect of (-)-Epigallocatechin-3-gallate on the in vitro growth of bovine Babesia parasites and the in vivo growth of the mouse-adapted rodent babesia B. microti. The in vitro growth of the Babesia species was significantly (P<0·05) inhibited in the presence of micromolar concentrations of EGCG (IC50 values=18 and 25 μM for B. bovis, and B. bigemina, respectively). The parasites showed no re-growth at 25 μM for B. bovis and B. bigemina in the subsequent viability test. The drug significantly (P<0·05) inhibited the growth of B. microti at doses of 5 and 10 mg/kg body weight, and the parasites completely cleared on day 14 and 16 post-inoculation in the 5 and 10 mg/kg treated groups, respectively. These findings highlight the potentiality of (-)-Epigallocatechin-3-gallate as a chemotherapeutic drug for the treatment of babesiosis.

Download Full-text

Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance

Pharmaceuticals ◽

10.3390/ph14050470 ◽

2021 ◽

Vol 14 (5) ◽

pp. 470

Author(s):

Nirmala Tilija Pun ◽

Chul-Ho Jeong

Keyword(s):

Cell Proliferation ◽

Drug Resistance ◽

Drug Repurposing ◽

Synergistic Action ◽

Cancer Drug ◽

Cancer Cell Proliferation ◽

Cancer Drug Resistance ◽

Anti Cancer

Cancer is incurable because progressive phenotypic and genotypic changes in cancer cells lead to resistance and recurrence. This indicates the need for the development of new drugs or alternative therapeutic strategies. The impediments associated with new drug discovery have necessitated drug repurposing (i.e., the use of old drugs for new therapeutic indications), which is an economical, safe, and efficacious approach as it is emerged from clinical drug development or may even be marketed with a well-established safety profile and optimal dosing. Statins are inhibitors of HMG-CoA reductase in cholesterol biosynthesis and are used in the treatment of hypercholesterolemia, atherosclerosis, and obesity. As cholesterol is linked to the initiation and progression of cancer, statins have been extensively used in cancer therapy with a concept of drug repurposing. Many studies including in vitro and in vivo have shown that statin has been used as monotherapy to inhibit cancer cell proliferation and induce apoptosis. Moreover, it has been used as a combination therapy to mediate synergistic action to overcome anti-cancer drug resistance as well. In this review, the recent explorations are done in vitro, in vivo, and clinical trials to address the action of statin either single or in combination with anti-cancer drugs to improve the chemotherapy of the cancers were discussed. Here, we discussed the emergence of statin as a lipid-lowering drug; its use to inhibit cancer cell proliferation and induction of apoptosis as a monotherapy; and its use in combination with anti-cancer drugs for its synergistic action to overcome anti-cancer drug resistance. Furthermore, we discuss the clinical trials of statins and the current possibilities and limitations of preclinical and clinical investigations.

Download Full-text

In silico drug repurposing of anticancer drug 5-FU and analogues against SARS-CoV-2 main protease

10.26434/chemrxiv-2021-gk1gt ◽

2021 ◽

Author(s):

Aristote Matondo ◽

Washington Dendera ◽

Bienfait K. Isamura ◽

Koto-te-Nyiwa Ngbolua ◽

Hilaire V.S. Mambo ◽

...

Keyword(s):

Drug Repurposing ◽

Pharmacological Action ◽

Time Saving ◽

Therapeutic Uses ◽

Main Protease ◽

Approved Drugs ◽

Effective Drugs ◽

Therapeutic Profile

The pressing need to find effective drugs against the current deadly COVID-19 disease has recently motivated numerous studies using different approaches to address the problem. One time-saving and less costly strategy is the drug repurposing, which consists in finding new therapeutic uses for approved drugs. Following the same trend, this study has investigated the potential inhibitory activity of 5-FU and its analogues against the SARS-CoV-2 main protease as well as their profile of druggability using molecular docking and ADMET methods. From the calculations performed, four candidates showed promising results with respect to the binding affinity to the target protease, 3CLpro, the therapeutic profile of druggability and safety. Further in-vitro and in-vivo investigations are needed that may clarify their possible mechanism of the pharmacological action to combat COVID-19.

Download Full-text

Molecular Docking in Formulation and Development

Current Drug Discovery Technologies ◽

10.2174/1570163815666180219112421 ◽

2019 ◽

Vol 16 (1) ◽

pp. 30-39 ◽

Cited By ~ 1

Author(s):

Tejinder Kaur ◽

Ashwini Madgulkar ◽

Mangesh Bhalekar ◽

Kalyani Asgaonkar

Keyword(s):

Molecular Docking ◽

Drug Discovery ◽

Dosage Form ◽

Development Process ◽

Critical Role ◽

Docking Studies ◽

Extensive Literature ◽

Time Saving ◽

Drug Discovery And Development

Background: In pharmaceutical research drug discovery and development process is timeconsuming and expensive. In many cases, it produces incompetent results due to the failure of in vitro and in vivo conventional approaches. Before any new drug is placed in the market it must undergo rigorous testing to get FDA approval. Due to the several limitations imposed by the drug discovery process, in recent times in silico approaches are widely applied in this field. The purpose of this review is to highlight the current molecular docking strategies used in drug discovery and to explore various advances in the field. Methods: In this review we have compiled database after an extensive literature search on docking studies which has found its applications relevant to the field of formulation and development. The papers retrieved were further screened to appraise the quality of work. In depth strategic analysis was carried out to confirm the credibility of the findings. Results: The papers included in this review highlight the promising role of docking studies to overcome the challenges in formulation and development by emphasizing it’s applications to predict drug excipient interactions which in turn assist to increase protein stability; to determine enzyme peptide interactions which maybe further used in drug development studies; to determine the most stable drug inclusion complex; to analyze structure at molecular level that ascertain an increase in solubility, dissolution and in turn the bioavailability of the drug; to design a dosage form that amplify the drug discovery and development process. Conclusion: This review summarizes recent findings of critical role played by molecular docking in the process of drug discovery and development. The application of docking approach will assist to design a dosage form in the most cost effective and time saving manner.

Download Full-text

Repurposing Old Drugs into New Epigenetic Inhibitors: Promising Candidates for Cancer Treatment?

Pharmaceutics ◽

10.3390/pharmaceutics12050410 ◽

2020 ◽

Vol 12 (5) ◽

pp. 410 ◽

Cited By ~ 5

Author(s):

Filipa Moreira-Silva ◽

Vânia Camilo ◽

Vítor Gaspar ◽

João F. Mano ◽

Rui Henrique ◽

...

Keyword(s):

Cancer Treatment ◽

Drug Repurposing ◽

Inhibitory Effect ◽

Epigenetic Alterations ◽

Effective Strategies ◽

Epigenetic Machinery ◽

Traditional Drug ◽

Repurposed Drugs ◽

Old Drugs

Epigenetic alterations, as a cancer hallmark, are associated with cancer initiation, progression and aggressiveness. Considering, however, that these alterations are reversible, drugs that target epigenetic machinery may have an inhibitory effect upon cancer treatment. The traditional drug discovery pathway is time-consuming and expensive, and thus, new and more effective strategies are required. Drug Repurposing (DR) comprises the discovery of a new medical indication for a drug that is approved for another indication, which has been recalled, that was not accepted or failed to prove efficacy. DR presents several advantages, mainly reduced resources, absence of the initial target discovery process and the reduced time necessary for the drug to be commercially available. There are numerous old drugs that are under study as repurposed epigenetic inhibitors which have demonstrated promising results in in vitro tumor models. Herein, we summarize the DR process and explore several repurposed drugs with different epigenetic targets that constitute promising candidates for cancer treatment, highlighting their mechanisms of action.

Download Full-text

Prospects for repurposing CNS drugs for cancer treatment

Oncology Reviews ◽

10.4081/oncol.2019.411 ◽

2019 ◽

Vol 13 (1) ◽

Cited By ~ 7

Author(s):

Mohamed Abdelaleem ◽

Hossam Ezzat ◽

Muhammed Osama ◽

Adel Megahed ◽

Waleed Alaa ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Drug Repurposing ◽

New Approach ◽

Central Nervous System Drugs ◽

Anti Cancer ◽

Cns Drugs ◽

New Anticancer Drugs

Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drugs over the last 8 years period (2010-2018) and including only evidence from Q1 journals as indicated by Scimago website (www.scimagojr.com). We concluded that Some Central Nervous system drugs show a great potential as anti-cancer in vitro, in vivo and clinical trials through different mechanisms and pathways in different types of cancer that reveal a promising evidence for the repurposing of CNS drugs for new indications.

Download Full-text