In vitro, in silico and in vivo screening of non-oncology drugs for repurposing in osteosarcoma

Prafulla Choudharı

Makale detayları

In vitro, in silico and in vivo screening of non-oncology drugs for repurposing in osteosarcoma

Yazarlar:

Prafulla Choudharı

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.27 Issue 2, pp.712-721

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347835

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 The first-line chemotherapy is associated with chief shortfalls such as non-specific distribution causing severe dose-dependent toxicities and development of tumor resistance. The current preliminary study aimed to identify the safe and effective non-oncology drugs as an alternative to toxic chemotherapeutics to treat osteosarcoma, and overcome new drugs shortage and development challenges. The different category non-oncology drugs alone and in combinations were screened for in vitro cytotoxicity behavior via MTT dye reduction assay and cell cycle arresting behavior using flow cytometer against human osteosarcoma Saos-2 and MG-63 cells. The molecular docking of selected therapeutics was executed against cyclin-dependent kinase 1 CDK1, cell cycle regulator overexpressed in cancer. The identified combination was further tested for in vivo toxicities in rats at two different doses. The current study revealed niclosamide NSD, ketoconazole KCZ, simvastatin SVN combination that causes substantial cytotoxicity IC50 values are in picomoles at 1:1:3 molar ratio when compared to other molar ratios. This combination has also caused substantial arrest of Saos-2 and MG-63 cells at S and G2M phase. Additionally, all three drugs demonstrated better interaction with CDK1 indicating anticancer potential via inhibition of CDK1. Furthermore, the in vivo toxicity study revealed no significant changes in hematological and biochemical parameters, body weights of rats, weights of vital organs, daily food and water intake, and general behavior of rats. The obtained preliminary results revealed the potential application of this combination on non-oncology drugs in the safe and effective treatment of osteosarcoma. However, further in-depth studies are required before clinical application.

 The first-line chemotherapy is associated with chief shortfalls such as non-specific distribution causing severe dose-dependent toxicities and development of tumor resistance. The current preliminary study aimed to identify the safe and effective non-oncology drugs as an alternative to toxic chemotherapeutics to treat osteosarcoma, and overcome new drugs shortage and development challenges. The different category non-oncology drugs alone and in combinations were screened for in vitro cytotoxicity behavior via MTT dye reduction assay and cell cycle arresting behavior using flow cytometer against human osteosarcoma Saos-2 and MG-63 cells. The molecular docking of selected therapeutics was executed against cyclin-dependent kinase 1 CDK1, cell cycle regulator overexpressed in cancer. The identified combination was further tested for in vivo toxicities in rats at two different doses. The current study revealed niclosamide NSD, ketoconazole KCZ, simvastatin SVN combination that causes substantial cytotoxicity IC50 values are in picomoles at 1:1:3 molar ratio when compared to other molar ratios. This combination has also caused substantial arrest of Saos-2 and MG-63 cells at S and G2M phase. Additionally, all three drugs demonstrated better interaction with CDK1 indicating anticancer potential via inhibition of CDK1. Furthermore, the in vivo toxicity study revealed no significant changes in hematological and biochemical parameters, body weights of rats, weights of vital organs, daily food and water intake, and general behavior of rats. The obtained preliminary results revealed the potential application of this combination on non-oncology drugs in the safe and effective treatment of osteosarcoma. However, further in-depth studies are required before clinical application.

 The first-line chemotherapy is associated with chief shortfalls such as non-specific distribution causing severe dose-dependent toxicities and development of tumor resistance. The current preliminary study aimed to identify the safe and effective non-oncology drugs as an alternative to toxic chemotherapeutics to treat osteosarcoma, and overcome new drugs shortage and development challenges. The different category non-oncology drugs alone and in combinations were screened for in vitro cytotoxicity behavior via MTT dye reduction assay and cell cycle arresting behavior using flow cytometer against human osteosarcoma Saos-2 and MG-63 cells. The molecular docking of selected therapeutics was executed against cyclin-dependent kinase 1 CDK1, cell cycle regulator overexpressed in cancer. The identified combination was further tested for in vivo toxicities in rats at two different doses. The current study revealed niclosamide NSD, ketoconazole KCZ, simvastatin SVN combination that causes substantial cytotoxicity IC50 values are in picomoles at 1:1:3 molar ratio when compared to other molar ratios. This combination has also caused substantial arrest of Saos-2 and MG-63 cells at S and G2M phase. Additionally, all three drugs demonstrated better interaction with CDK1 indicating anticancer potential via inhibition of CDK1. Furthermore, the in vivo toxicity study revealed no significant changes in hematological and biochemical parameters, body weights of rats, weights of vital organs, daily food and water intake, and general behavior of rats. The obtained preliminary results revealed the potential application of this combination on non-oncology drugs in the safe and effective treatment of osteosarcoma. However, further in-depth studies are required before clinical application.

 The first-line chemotherapy is associated with chief shortfalls such as non-specific distribution causing severe dose-dependent toxicities and development of tumor resistance. The current preliminary study aimed to identify the safe and effective non-oncology drugs as an alternative to toxic chemotherapeutics to treat osteosarcoma, and overcome new drugs shortage and development challenges. The different category non-oncology drugs alone and in combinations were screened for in vitro cytotoxicity behavior via MTT dye reduction assay and cell cycle arresting behavior using flow cytometer against human osteosarcoma Saos-2 and MG-63 cells. The molecular docking of selected therapeutics was executed against cyclin-dependent kinase 1 CDK1, cell cycle regulator overexpressed in cancer. The identified combination was further tested for in vivo toxicities in rats at two different doses. The current study revealed niclosamide NSD, ketoconazole KCZ, simvastatin SVN combination that causes substantial cytotoxicity IC50 values are in picomoles at 1:1:3 molar ratio when compared to other molar ratios. This combination has also caused substantial arrest of Saos-2 and MG-63 cells at S and G2M phase. Additionally, all three drugs demonstrated better interaction with CDK1 indicating anticancer potential via inhibition of CDK1. Furthermore, the in vivo toxicity study revealed no significant changes in hematological and biochemical parameters, body weights of rats, weights of vital organs, daily food and water intake, and general behavior of rats. The obtained preliminary results revealed the potential application of this combination on non-oncology drugs in the safe and effective treatment of osteosarcoma. However, further in-depth studies are required before clinical application.

Makale detayları

In vitro, in silico and in vivo screening of non-oncology drugs for repurposing in osteosarcoma

Yazarlar:

Prafulla Choudharı

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.27 Issue 2, pp.712-721

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347835

pISSN:

2630-6344

Drug repurposing

osteosarcoma

cytotoxicity

molecular docking

acute toxicity

Sayı

Makale detayları

In vitro, in silico and in vivo screening of non-oncology drugs for repurposing in osteosarcoma

Yazarlar: Prafulla Choudharı

Yayıncı: Marmara University

Ana Başlıklar: Pharmaceutical Chemistry

Dergi: Journal of Research in Pharmacy Vol.27 Issue 2, pp.712-721

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001347835

pISSN: 2630-6344

Drug repurposing

osteosarcoma

cytotoxicity

molecular docking

acute toxicity

Sayı

Yazarlar:

Prafulla Choudharı

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.27 Issue 2, pp.712-721

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347835

pISSN:

2630-6344