Bioisosteric replacements of tyrosine kinases inhibitors to make potent and safe chemotherapy against malignant cells
The liver function test is an imperative element in chemotherapy management due to the idiosyncratic reaction of chemotherapy drugs. This study primly aimed to replace the toxic fragments of known protein tyrosine kinases inhibitors (PTKi) to develop safe and effective chemotherapy. All the current PTKi's were docked with the tyrosine kinases and metabolic enzymes to study the affinities on the target. It resulted from most of the PTKi's found higher affinity and efficacy with metabolic enzymes lead the hepatic cells damage. To overcome this limitation of PTKi's, a bioisosteric replacement strategy was achieved and conceptual analogs were designed. Specifically, the Generated pose of the Axitinib molecule showed that axitinib fragments C = C-, -C = O and NH2 produced clashes with active site residues of tyrosine kinases protein and good affinity with metabolic enzyme primes to the liver toxicity. The above said fragments were replaced with various bioisosteric groups and efficacy was measured. The resulting molecule shows improved affinity with tyrosine kinases enzyme and less interactions with metabolic enzyme were imminent molecule for the treatment of malignant cells with outside effects.Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
|---|---|
| Enthalten in: |
Journal of biomolecular structure & dynamics - 41(2023), 19 vom: 01. Nov., Seite 9437-9447 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Irfan, Navabshan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
42HK56048U |
|---|
| Anmerkungen: |
Date Completed 30.10.2023 Date Revised 01.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/07391102.2022.2146751 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM349290318 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM349290318 | ||
| 003 | DE-627 | ||
| 005 | 20231226042254.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/07391102.2022.2146751 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1164.xml |
| 035 | |a (DE-627)NLM349290318 | ||
| 035 | |a (NLM)36415919 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Irfan, Navabshan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Bioisosteric replacements of tyrosine kinases inhibitors to make potent and safe chemotherapy against malignant cells |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.10.2023 | ||
| 500 | |a Date Revised 01.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The liver function test is an imperative element in chemotherapy management due to the idiosyncratic reaction of chemotherapy drugs. This study primly aimed to replace the toxic fragments of known protein tyrosine kinases inhibitors (PTKi) to develop safe and effective chemotherapy. All the current PTKi's were docked with the tyrosine kinases and metabolic enzymes to study the affinities on the target. It resulted from most of the PTKi's found higher affinity and efficacy with metabolic enzymes lead the hepatic cells damage. To overcome this limitation of PTKi's, a bioisosteric replacement strategy was achieved and conceptual analogs were designed. Specifically, the Generated pose of the Axitinib molecule showed that axitinib fragments C = C-, -C = O and NH2 produced clashes with active site residues of tyrosine kinases protein and good affinity with metabolic enzyme primes to the liver toxicity. The above said fragments were replaced with various bioisosteric groups and efficacy was measured. The resulting molecule shows improved affinity with tyrosine kinases enzyme and less interactions with metabolic enzyme were imminent molecule for the treatment of malignant cells with outside effects.Communicated by Ramaswamy H. Sarma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a PTKi’s | |
| 650 | 4 | |a SeeSAR | |
| 650 | 4 | |a chemotherapy | |
| 650 | 4 | |a hepatotoxicity | |
| 650 | 4 | |a tyrosine kinases | |
| 650 | 7 | |a Axitinib |2 NLM | |
| 650 | 7 | |a C9LVQ0YUXG |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Protein-Tyrosine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Tyrosine |2 NLM | |
| 650 | 7 | |a 42HK56048U |2 NLM | |
| 700 | 1 | |a Balasubramaniyan, Sakthivel |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Davoodbasha Mubarak |e verfasserin |4 aut | |
| 700 | 1 | |a Puratchikody, Ayarivan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of biomolecular structure & dynamics |d 1985 |g 41(2023), 19 vom: 01. Nov., Seite 9437-9447 |w (DE-627)NLM012639974 |x 1538-0254 |7 nnns |
| 773 | 1 | 8 | |g volume:41 |g year:2023 |g number:19 |g day:01 |g month:11 |g pages:9437-9447 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/07391102.2022.2146751 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 41 |j 2023 |e 19 |b 01 |c 11 |h 9437-9447 | ||