Synergistic combination of ritonavir and cisplatin as an efficacious therapy in human cervical cancer cells: a computational drug discovery and<i>in vitro</i>insight

Swami, Dayanand; Mudaliar, Priyanka; Bichu, Yash Shrinivas; Sahu, Vishal Kumar; Devarajan, Shine; Basu, Soumya; Aich, Jyotirmoi

doi:10.1080/07391102.2022.2097312

Cited by 3 publications

(4 citation statements)

References 89 publications

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“…Cell-based cytotoxicity assay was performed in accordance with a prior study [32] conducted with minor modifications to determine the percentage viability of cells and to observe the related morphological alterations in the cells. Cells were seeded with 5000 cells/well in 96-well ELISA plates followed by incubation with different dilutions of the drug telmisartan for a duration of 48 h. Dimethyl sulfoxide (DMSO) was used to prepare the Stock concentration of telmisartan.…”

Section: Methodsmentioning

confidence: 99%

Exploring the repurposing potential of telmisartan drug in breast cancer: an in-silico and in-vitro approach

2023

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Anticancer drug resistance is one of the biggest hurdles in the treatment of breast cancer. Drug repurposing is a viable option fordeveloping novel medical treatment strategies since this method is more cost-efficient and rapid. Antihypertensive medicines have recently been found to have pharmacological features that could be used to treat cancer, making them effective candidates for therapeutic repurposing. The goal of our research is to find a potent antihypertensive drug that can be repurposed as adjuvant therapy for breast cancer. In this study, virtual screening was performed using a set of Food and Drug Administration (FDA)-approved antihypertensive drugs as ligands with selected receptor proteins (EGFR, KRAS, P53, AGTR1, AGTR2, and ACE) assuming these proteins are regarded to have a significant role in hypertension as well as breast cancer. Further, our in-silico results were further confirmed by an in-vitro experiment (cytotoxicity assay). All the compounds (enalapril, atenolol, acebutolol, propranolol, amlodipine, verapamil, doxazosin, prazosin, hydralazine, irbesartan, telmisartan, candesartan, and aliskiren) showed remarkable affinity towards the target receptor proteins. However, maximum affinity was displayed by telmisartan. Cell-based cytotoxicity study of telmisartan in MCF7 (breast cancer cell line) confirmed the anticancer effect of telmisartan. IC50 of the drug was calculated to be 7.75 µM and at this concentration, remarkable morphological alterations were observed in the MCF7 cells confirming its cytotoxicity in breast cancer cells. Based on both in-silico and in-vitro studies, we can conclude that telmisartan appears to be a promising drug repurposing candidate for the therapeutic treatment of breast cancer.

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Section: Methodsmentioning

confidence: 99%

Exploring the repurposing potential of telmisartan drug in breast cancer: an in-silico and in-vitro approach

2023

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“…To understand and repurpose Ritonavir and its combination with cisplatin, VS was performed to find drug-target binding affinity and DTI of Ritonavir with alternative proteins. 266…”

Section: Hiv Type 1 (Hiv-1 or Hiv)mentioning

confidence: 99%

“…To understand and repurpose Ritonavir and its combination with cisplatin, VS was performed to find drug‐target binding affinity and DTI of Ritonavir with alternative proteins 266 . Results showed that Ritonavir exhibited highest binding affinity against CYP450 3A4, PDGFR and ALK.…”

Section: ML Dl and Other Drug Repurposing Approachesmentioning

confidence: 99%

Drug repurposing for viral cancers: A paradigm of machine learning, deep learning, and virtual screening‐based approaches

Ahmed

Kang

Kim

et al. 2023

Journal of Medical Virology

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Cancer management is major concern of health organizations and viral cancers account for approximately 15.4% of all known human cancers. Due to large number of patients, efficient treatments for viral cancers are needed. De novo drug discovery is time consuming and expensive process with high failure rate in clinical stages. To address this problem and provide treatments to patients suffering from viral cancers faster, drug repurposing emerges as an effective alternative which aims to find the other indications of the Food and Drug Administration approved drugs. Applied to viral cancers, drug repurposing studies following the niche have tried to find if already existing drugs could be used to treat viral cancers. Multiple drug repurposing approaches till date have been introduced with successful results in viral cancers and many drugs have been successfully repurposed various viral cancers.Here in this study, a critical review of viral cancer related databases, tools, and different machine learning, deep learning and virtual screening-based drug repurposing studies focusing on viral cancers is provided. Additionally, the mechanism of viral cancers is presented along with drug repurposing case study specific to each viral cancer. Finally, the limitations and challenges of various approaches along with possible solutions are provided.antihepatitis B virus antivirals, antiviral agents, artificial intelligence, drug repurposing, rational drug design | INTRODUCTIONDrug repurposing (also referred to as drug repositioning, drug reprofiling, drug redirecting, drug rescue and more 1 ) is a method for finding new indications beyond the scope of original indications of already approved drugs. 2 A conventional method of drug discovery is quite time taking and expensive task. Time required for a de novo drug is 12-17 years with an estimated expense of $2-$3 billion whereas the success rate is less than 10%. 3 This renders de novo drug discovery a risky process. Drug repurposing is an effective alternative to de novo drug discovery and offers many benefits such as reducing the time and money required to 5-7 years 4,5 and $200-$300 million, respectively, since much of the toxicity and efficacy information is already known. It also increases the success rate in clinical development and testing phases. 6 Success stories of drug repurposing have resulted in serendipity and by physicians' observation. 7 One such example is

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“…Other antiretrovirals have also been studied in relation to cancer. Other PIs like DRV that have been shown to exhibit effects include ritonavir (in treating cervical cancer) [109] and nelfinavir (in treating pancreatic cancer) [110]. These drugs provide direct evidence both through in silico methods and in cancer cells, while DRV's effect is still only theoretical.…”

Section: Repurposing For Cancer Treatmentmentioning

confidence: 99%

A Review Concerning the Use of Etravirine and Darunavir in Translational Medicine

Pereira,

Vale

2023

IJTM

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This comprehensive review explores two antiretroviral drugs, Etravirine (ETV) and Darunavir (DRV), a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor, that are commonly used in human immunodeficiency virus (HIV) infection treatment, often in combination with each other. The pharmacokinetic properties of these drugs are covered as well as the clinical trials of these two drugs combined. This paper also delves into the possible repurposing of these two drugs for other diseases, with drug repurposing being a significant factor in addressing global health challenges. DRV was extensively studied for treating COVID-19, as well as other infections, such as candidiasis and cryptococcosis, while ETV proved to be efficient in hampering Zika virus brain infection. The focus on cancer repurposing is also explored, with the results revealing that ETV has a particular inhibitory effect on ovarian cancer in vitro and on cancer molecules, such as anterior gradient protein 2 homolog (AGR2) and casein kinase 1 (CK1ε), and that DRV has an in silico inhibitory effect on human lactate dehydrogenase A (LDHA) and induces the in vitro and in vivo inhibition of pepsin, consequent laryngopharyngeal reflux, and possible laryngeal and hypopharyngeal carcinomas. The significance of fresh methods of drug development is emphasized in this work, as is the enormous potential for new therapeutic uses of the antiretroviral drugs ETV and DRV in viral and non-viral disorders.

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Synergistic combination of ritonavir and cisplatin as an efficacious therapy in human cervical cancer cells: a computational drug discovery andin vitroinsight

Cited by 3 publications

References 89 publications

Exploring the repurposing potential of telmisartan drug in breast cancer: an in-silico and in-vitro approach

Exploring the repurposing potential of telmisartan drug in breast cancer: an in-silico and in-vitro approach

Drug repurposing for viral cancers: A paradigm of machine learning, deep learning, and virtual screening‐based approaches

A Review Concerning the Use of Etravirine and Darunavir in Translational Medicine

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