A facile in silico drug design strategy based on reference  listed drugs and computational modeling of novel  anticancer therapeutics

Asha Thomas

Makale detayları

A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics

Yazarlar:

Asha Thomas

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.23 Issue 6, pp.1067-1078

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347955

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 Heterocyclic compounds present unique structural and physicochemical diversity. Especially, the aromatic heterocycliccompounds like indole exhibit anti-cancer properties by facilitating cancerous cell death. Drug discovery and development process relyto a large extent on the in silico identification of the putative targets and rational design of potentially therapeutic ligands. We propose a facile strategy of in silico drug designing hereby curating libraries having a functional group modification of the indole heterocyclic compounds with 2-chloro-N-2-chloroethyl N-methylethanamine. Subsequently, we compare the designed drugs with the existing alkylating Reference Listed Drugs RLDs of the USFDA. We computationally model the indole ring as a basic scaffold and induce 2-chloro-N-2 chloroethyl-N-methylethanamine substitution on the C-3 of indole with experimentally available target DNA receptor to design an extensive library of 200 molecules. This was followed by extensive ligand-DNA docking studies to predict putative targets andADMET prediction of an optimized ligand. Our simple in silico strategy reveals that the designed compounds such as AGSPBM134, AGSPBM133, AGSPBM131, AGSPBM130, AGSPBM132 and AGSPBM019 exhibitstructural similarity towards the RLD as shown by ECFP-6 fingerprints. We show that they pass all the similarity criteria of the physicochemical parameters with no violation of the Lipinskis rule of five. We positthat these agents can potentially be a good choice for further synthesis in the development of novel anti-cancer agents.

 Heterocyclic compounds present unique structural and physicochemical diversity. Especially, the aromatic heterocycliccompounds like indole exhibit anti-cancer properties by facilitating cancerous cell death. Drug discovery and development process relyto a large extent on the in silico identification of the putative targets and rational design of potentially therapeutic ligands. We propose a facile strategy of in silico drug designing hereby curating libraries having a functional group modification of the indole heterocyclic compounds with 2-chloro-N-2-chloroethyl N-methylethanamine. Subsequently, we compare the designed drugs with the existing alkylating Reference Listed Drugs RLDs of the USFDA. We computationally model the indole ring as a basic scaffold and induce 2-chloro-N-2 chloroethyl-N-methylethanamine substitution on the C-3 of indole with experimentally available target DNA receptor to design an extensive library of 200 molecules. This was followed by extensive ligand-DNA docking studies to predict putative targets andADMET prediction of an optimized ligand. Our simple in silico strategy reveals that the designed compounds such as AGSPBM134, AGSPBM133, AGSPBM131, AGSPBM130, AGSPBM132 and AGSPBM019 exhibitstructural similarity towards the RLD as shown by ECFP-6 fingerprints. We show that they pass all the similarity criteria of the physicochemical parameters with no violation of the Lipinskis rule of five. We positthat these agents can potentially be a good choice for further synthesis in the development of novel anti-cancer agents.

 Heterocyclic compounds present unique structural and physicochemical diversity. Especially, the aromatic heterocycliccompounds like indole exhibit anti-cancer properties by facilitating cancerous cell death. Drug discovery and development process relyto a large extent on the in silico identification of the putative targets and rational design of potentially therapeutic ligands. We propose a facile strategy of in silico drug designing hereby curating libraries having a functional group modification of the indole heterocyclic compounds with 2-chloro-N-2-chloroethyl N-methylethanamine. Subsequently, we compare the designed drugs with the existing alkylating Reference Listed Drugs RLDs of the USFDA. We computationally model the indole ring as a basic scaffold and induce 2-chloro-N-2 chloroethyl-N-methylethanamine substitution on the C-3 of indole with experimentally available target DNA receptor to design an extensive library of 200 molecules. This was followed by extensive ligand-DNA docking studies to predict putative targets andADMET prediction of an optimized ligand. Our simple in silico strategy reveals that the designed compounds such as AGSPBM134, AGSPBM133, AGSPBM131, AGSPBM130, AGSPBM132 and AGSPBM019 exhibitstructural similarity towards the RLD as shown by ECFP-6 fingerprints. We show that they pass all the similarity criteria of the physicochemical parameters with no violation of the Lipinskis rule of five. We positthat these agents can potentially be a good choice for further synthesis in the development of novel anti-cancer agents.

 Heterocyclic compounds present unique structural and physicochemical diversity. Especially, the aromatic heterocycliccompounds like indole exhibit anti-cancer properties by facilitating cancerous cell death. Drug discovery and development process relyto a large extent on the in silico identification of the putative targets and rational design of potentially therapeutic ligands. We propose a facile strategy of in silico drug designing hereby curating libraries having a functional group modification of the indole heterocyclic compounds with 2-chloro-N-2-chloroethyl N-methylethanamine. Subsequently, we compare the designed drugs with the existing alkylating Reference Listed Drugs RLDs of the USFDA. We computationally model the indole ring as a basic scaffold and induce 2-chloro-N-2 chloroethyl-N-methylethanamine substitution on the C-3 of indole with experimentally available target DNA receptor to design an extensive library of 200 molecules. This was followed by extensive ligand-DNA docking studies to predict putative targets andADMET prediction of an optimized ligand. Our simple in silico strategy reveals that the designed compounds such as AGSPBM134, AGSPBM133, AGSPBM131, AGSPBM130, AGSPBM132 and AGSPBM019 exhibitstructural similarity towards the RLD as shown by ECFP-6 fingerprints. We show that they pass all the similarity criteria of the physicochemical parameters with no violation of the Lipinskis rule of five. We positthat these agents can potentially be a good choice for further synthesis in the development of novel anti-cancer agents.

Makale detayları

A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics

Yazarlar:

Asha Thomas

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.23 Issue 6, pp.1067-1078

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347955

pISSN:

2630-6344

Indole

drug designing

molecular docking

computer-aided drug designing

ADMET

Sayı

Makale detayları

A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics

Yazarlar: Asha Thomas

Yayıncı: Marmara University

Ana Başlıklar: Pharmaceutical Chemistry

Dergi: Journal of Research in Pharmacy Vol.23 Issue 6, pp.1067-1078

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001347955

pISSN: 2630-6344

Indole

drug designing

molecular docking

computer-aided drug designing

ADMET

Sayı

Yazarlar:

Asha Thomas

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.23 Issue 6, pp.1067-1078

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347955

pISSN:

2630-6344