7 Identification of potential inhibitors of thymidylate synthase (TS) (PDB ID: 6QXH) and nuclear factor kappa-B (NF–κB) (PDB ID: 1A3Q) from Capsicum annuum (bell pepper) towards the development of new therapeutic drugs against colorectal cancer (CRC)
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Misbaudeen Abdul-Hammed
Abstract
Colorectal cancer is the third most deadly cancer globally. Drug resistance and attendant side effects make the available standard anti-colorectal cancer drugs against target receptors inefficient. Phytochemicals from medicinal plants are safer, cheaper, effective, and heal diseases from the cellular level. This study is aimed at identifying potential inhibitors of thymidylate synthase (TS) and nuclear factor kappa- B (NF-κB) target receptors from Capsicum annuum towards the development of new therapeutic drugs against colorectal cancer via in silico approach. One hundred and fifty (150) ligands previously reported from Capsicum annuum were downloaded from the PubChem database and were subjected to chemo-informatics analyses such as ADMET, drug-likeness, oral bioavailability, bioactivity, and PASS prediction to ascertain their therapeutic and safety profile before docking. The ligands that passed the analyses were docked against TS and NF-κB in duplicate using a creditable docking tool (PyRx). Raltitrexed and emetine were used as the standard drug inhibitors for TS and NF-κB, respectively. The results obtained from this study showed that feruloylbeta- D-glucose (8.45 kcal/mol), 5-O-caffeoylquinic acid (−8.40 kcal/mol), 5-O-caffeoylquinic acid methyl ester (−7.89 kcal/mol), feruloyl hexoside (−7.40 kcal/mol), O-glucopyranoside (−7.55 kcal/mol), and quercetin (−7.00 kcal/mol) shared the same binding pocket with TS while feruloyl-beta-D-glucose (−7.00 kcal/mol), chlorogenic acid (−6.90 kcal/mol), 5-O-caffeoylquinic acid (−6.90 kcal/mol) and feruloyl hexoside (−6.50 kcal/mol) shared the same pocket with NF-κB. These compounds were selected as best hits due to their excellent inhibitory efficiency and chemoinformatic profiles. Thus, the compounds may function as prospective lead compounds for developing a new anti-colorectal cancer drug.
Abstract
Colorectal cancer is the third most deadly cancer globally. Drug resistance and attendant side effects make the available standard anti-colorectal cancer drugs against target receptors inefficient. Phytochemicals from medicinal plants are safer, cheaper, effective, and heal diseases from the cellular level. This study is aimed at identifying potential inhibitors of thymidylate synthase (TS) and nuclear factor kappa- B (NF-κB) target receptors from Capsicum annuum towards the development of new therapeutic drugs against colorectal cancer via in silico approach. One hundred and fifty (150) ligands previously reported from Capsicum annuum were downloaded from the PubChem database and were subjected to chemo-informatics analyses such as ADMET, drug-likeness, oral bioavailability, bioactivity, and PASS prediction to ascertain their therapeutic and safety profile before docking. The ligands that passed the analyses were docked against TS and NF-κB in duplicate using a creditable docking tool (PyRx). Raltitrexed and emetine were used as the standard drug inhibitors for TS and NF-κB, respectively. The results obtained from this study showed that feruloylbeta- D-glucose (8.45 kcal/mol), 5-O-caffeoylquinic acid (−8.40 kcal/mol), 5-O-caffeoylquinic acid methyl ester (−7.89 kcal/mol), feruloyl hexoside (−7.40 kcal/mol), O-glucopyranoside (−7.55 kcal/mol), and quercetin (−7.00 kcal/mol) shared the same binding pocket with TS while feruloyl-beta-D-glucose (−7.00 kcal/mol), chlorogenic acid (−6.90 kcal/mol), 5-O-caffeoylquinic acid (−6.90 kcal/mol) and feruloyl hexoside (−6.50 kcal/mol) shared the same pocket with NF-κB. These compounds were selected as best hits due to their excellent inhibitory efficiency and chemoinformatic profiles. Thus, the compounds may function as prospective lead compounds for developing a new anti-colorectal cancer drug.
Kapitel in diesem Buch
- Frontmatter I
- Preface of the Book of Proceedings of the Virtual Conference on Chemistry and its Applications (VCCA-2022). V
- Contents VII
- List of contributing authors XIX
- 1 Dipeptidyl peptidase IV: a multifunctional enzyme with implications in several pathologies including cancer 1
- 2 A mini review on the prospects of Fagara zanthoxyloides extract based composites: a remedy for COVID-19 and associated replica? 57
- 3 Triterpenoids of antibacterial extracts from the leaves of Bersama abyssinica Fresen (Francoaceae) 75
- 4 Physicochemical assessment and insilico studies on the interaction of 5-HT2c receptor with herbal medication bioactive compounds used in the treatment of premature ejaculation 87
- 5 Xanthoangelol, geranilated chalcone compound, isolation from pudau leaves (Artocarpus kemando Miq.) as antibacterial and anticancer 121
- 6 Exploration of bioactive compounds from Mangifera indica (Mango) as probable inhibitors of thymidylate synthase and nuclear factor kappa-B (NF-Κb) in colorectal cancer management 137
- 7 Identification of potential inhibitors of thymidylate synthase (TS) (PDB ID: 6QXH) and nuclear factor kappa-B (NF–κB) (PDB ID: 1A3Q) from Capsicum annuum (bell pepper) towards the development of new therapeutic drugs against colorectal cancer (CRC) 165
- 8 Synthesis, characterization and in vitro activity study of some organotin(IV) carboxylates against leukemia cancer cell, L-1210 199
- 9 Phytochemicals from Annona muricata (Sour Sop) as potential inhibitors of SARS-CoV-2 main protease (Mpro) and spike receptor protein: a structure-based drug design studies and chemoinformatics analyses 207
- 10 Identification of novel inhibitors of P13K/AKT pathways: an integrated in-silico study towards the development of a new therapeutic agent against ovarian cancer 231
- 11 Immobilization of α-amylase from Aspergillus fumigatus using adsorption method onto zeolite 261
- 12 Phytochemical components and GC–MS analysis of Petiveria alliaceae L. fractions and volatile oils 273
- 13 Characterization of crude saponins from stem bark extract of Parinari curatellifolia and evaluation of its antioxidant and antibacterial activities 287
- 14 Physicochemical and free radical scavenging activity of Adansonia digitata seed oil 307
- 15 Photoprotection strategies with antioxidant extracts: a new vision 321
- 16 A systematic DFT study of arsenic doped iron cluster AsFen (n = 1–4) 335
- 17 Effect of case-based learning, team-based learning and regular teaching methods on secondary school students’ self-concept in chemistry in Maara sub-county, Tharaka Nithi county, Kenya 345
- 18 Random and block architectures of N-arylitaconimide monomers with methyl methacrylate 359
- 19 Evaluation of phytochemicals and amino acid profiles of four vegetables grown on a glyphosate contaminated soil in Southwestern Nigeria 399
- Index 411
Kapitel in diesem Buch
- Frontmatter I
- Preface of the Book of Proceedings of the Virtual Conference on Chemistry and its Applications (VCCA-2022). V
- Contents VII
- List of contributing authors XIX
- 1 Dipeptidyl peptidase IV: a multifunctional enzyme with implications in several pathologies including cancer 1
- 2 A mini review on the prospects of Fagara zanthoxyloides extract based composites: a remedy for COVID-19 and associated replica? 57
- 3 Triterpenoids of antibacterial extracts from the leaves of Bersama abyssinica Fresen (Francoaceae) 75
- 4 Physicochemical assessment and insilico studies on the interaction of 5-HT2c receptor with herbal medication bioactive compounds used in the treatment of premature ejaculation 87
- 5 Xanthoangelol, geranilated chalcone compound, isolation from pudau leaves (Artocarpus kemando Miq.) as antibacterial and anticancer 121
- 6 Exploration of bioactive compounds from Mangifera indica (Mango) as probable inhibitors of thymidylate synthase and nuclear factor kappa-B (NF-Κb) in colorectal cancer management 137
- 7 Identification of potential inhibitors of thymidylate synthase (TS) (PDB ID: 6QXH) and nuclear factor kappa-B (NF–κB) (PDB ID: 1A3Q) from Capsicum annuum (bell pepper) towards the development of new therapeutic drugs against colorectal cancer (CRC) 165
- 8 Synthesis, characterization and in vitro activity study of some organotin(IV) carboxylates against leukemia cancer cell, L-1210 199
- 9 Phytochemicals from Annona muricata (Sour Sop) as potential inhibitors of SARS-CoV-2 main protease (Mpro) and spike receptor protein: a structure-based drug design studies and chemoinformatics analyses 207
- 10 Identification of novel inhibitors of P13K/AKT pathways: an integrated in-silico study towards the development of a new therapeutic agent against ovarian cancer 231
- 11 Immobilization of α-amylase from Aspergillus fumigatus using adsorption method onto zeolite 261
- 12 Phytochemical components and GC–MS analysis of Petiveria alliaceae L. fractions and volatile oils 273
- 13 Characterization of crude saponins from stem bark extract of Parinari curatellifolia and evaluation of its antioxidant and antibacterial activities 287
- 14 Physicochemical and free radical scavenging activity of Adansonia digitata seed oil 307
- 15 Photoprotection strategies with antioxidant extracts: a new vision 321
- 16 A systematic DFT study of arsenic doped iron cluster AsFen (n = 1–4) 335
- 17 Effect of case-based learning, team-based learning and regular teaching methods on secondary school students’ self-concept in chemistry in Maara sub-county, Tharaka Nithi county, Kenya 345
- 18 Random and block architectures of N-arylitaconimide monomers with methyl methacrylate 359
- 19 Evaluation of phytochemicals and amino acid profiles of four vegetables grown on a glyphosate contaminated soil in Southwestern Nigeria 399
- Index 411
