Design and Development of Novel Hybrids Based on Pyrrolo[2,1-f][1,2,4]Triazine and 1-(Methylpiperidin-4-yl) Aniline-Based Analogs: Exploring the Utility as Anticancer Agents via MERTK Inhibition.
| Autor: | Sathe BD; Department of Chemistry, Bharatiya Vidya Bhavan College, Chowpatty, Mumbai University, Mumbai, India.; Integral Biosciences Pvt Ltd., Drug Discovery Biotech, Noida, India., Jaiswal S; Institute of Pharmaceutical Research, GLA University, Mathura, India., Kumar D; School of Pharmacy, Narsee Monjee Institute of Management Studies (NMIMS), Dhule, Maharashtra, India., Singh TG; Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India., Nainwal N; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, Uttarakhand, India., Rawat P; Department of Biotechnology, Graphic Era (Deemed to Be University), Dehradun, India.; Department of Biotechnology, Graphic Era Hill University, Dehradun, India., Yadav S; IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh, India., Kumar B; Department of Pharmaceutical Sciences, Chauras Campus, HNB Garhwal University (A Central University), Srinagar, Uttarakhand, India., Dwivedi AR; GITAM School of Pharmacy, GITAM (Deemed to Be) University, Hyderabad, India., Rathod SV; Department of Chemistry, Bharatiya Vidya Bhavan College, Chowpatty, Mumbai University, Mumbai, India. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Chemical biology & drug design [Chem Biol Drug Des] 2024 Dec; Vol. 104 (6), pp. e70023. |
| DOI: | 10.1111/cbdd.70023 |
| Abstrakt: | Mer-tyrosine kinase (MERTK), a member of the AXL, TYRO3, and MERTK (TAM) family, is one of the promising targets for cancer treatment. It plays a key role in cancer cell survival and proliferation and regulates immune responses in cancer. The study aimed to rationally design and develop molecules considering the pharmacophoric requirements of MERTK using a multi-synthetic approach followed by the hybridization of individual pharmacophores. A hybrid drug design approach was employed by hybridization of pyrrolo[2,1-f][1,2,4]triazine and 1-(methylpiperidin-4-yl)aniline pharmacophoric systems to develop novel leads (1K1-1K5). The molecules were synthesized via a multi-step synthetic approach. The synthesized molecules were assessed for their pharmacological potential via cell viability, drug metabolism and pharmacokinetics (DMPK), and MERTK inhibition studies corroborated by in silico studies. IK5 was found to have an IC (© 2024 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|
Plný text