Exploring the Antiproliferative Potency of Pyrido[2,3‐d]Pyrimidine Derivatives: Studies on Design, Synthesis, Anticancer Evaluation, SAR, Docking, and DFT Calculations DOI

Eman Abd‐Alsalam,

Hend N. Hafez,

M. G. Assay

et al.

Chemistry & Biodiversity, Journal Year: 2023, Volume and Issue: 21(2)

Published: Dec. 12, 2023

Abstract Herein, an efficient method for the synthesis of a new series pyrido[2,3‐ d ]pyrimidine derivatives has been adopted through reaction hydrazinyl ] pyrimidine derivative ( 1 ) with different electrophilic species, such as ethyl cyanoacetate and 1,3 diketone derivatives, gave corresponding 2 – 5 ). Meanwhile, ][1,2,4]triazolo[4,3‐ ]pyrimidines 6 11 were synthesized via hydrazine phenylisothiocyanate, potassium thiocyanate, carbon disulfide. Compound was also submitted to react carbonyl compounds afford pyrido‐pyrimidine 12 15 All newly tested in vitro their antiproliferative activities against HCT‐116 MCF‐7 cell lines. Compounds , 3 7 8 displayed very strong inhibitory activity two lines compared standard drug doxorubicin. Furthermore, docking study most active performed thymidylate synthase enzyme (PDB: Code 6qxg). Moreover, DFT calculation carried out biologically reference (Doxorubicin) using B3LYP/6‐31G+(d,p) level theory. The calculated E HOMO LUMO energies used calculate global reactivity parameters. Finally, Molecular electrostatic potential (MEP) structure relationship (SAR) studied correlate relation between chemical reactivity.

Language: Английский

Advances in pyrazolo[1,5-a]pyrimidines: synthesis and their role as protein kinase inhibitors in cancer treatment DOI Creative Commons

Terungwa H. Iorkula,

Osasere Jude-Kelly Osayawe,

Daniel A. Odogwu

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(5), P. 3756 - 3828

Published: Jan. 1, 2025

Pyrazolo[1,5- a ]pyrimidines are notable class of heterocyclic compounds with potent protein kinase inhibitor (PKI) activity, playing critical role in targeted cancer therapy.

Language: Английский

Citations

2
Some pyrimidohexahydroquinoline candidates: synthesis, DFT, cytotoxic activity evaluation, molecular docking, and in silico studies DOI Creative Commons
Sayed K. Ramadan, Hisham S. M. Abd‐Rabboh,

Amal A. Abdel Hafez

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(23), P. 16584 - 16599

Published: Jan. 1, 2024

Hexahydroquinolines were prepared and supported by in silico studies. Thiosemicarbazide thiazolidinone derivatives showed the highest vitro antiproliferative potency against liver, breast, prostate, colon cancer cell lines.

Language: Английский

Citations

14
Rationale design of novel substituted 1,3,5-triazine candidates as dual IDH1(R132H)/ IDH2(R140Q) inhibitors with high selectivity against acute myeloid leukemia: In vitro and in vivo preclinical investigations DOI
Haytham O. Tawfik, Mai H. A. Mousa, Mohamed Y. Zaky

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 149, P. 107483 - 107483

Published: May 21, 2024

Language: Английский

Citations

9
Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers DOI Creative Commons
Samar El‐Kalyoubi, Mohamed M. Khalifa, Mahmoud T. Abo‐Elfadl

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Aug. 18, 2023

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation spirooxindoles pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets SeNP examined their cytotoxicity towards five cancer cell lines. inhibitory potencies best members against I II also assayed besides DNA intercalation abilities. Compound 7d NPs exhibited inhibition enzymes with IC50 0.042 1.172 μM, respectively. ability compound to arrest cycle induce apoptosis investigated. It arrested in A549 at S phase prompted by 41.02% vs. 23.81% control. silico studies then performed study possible binding interactions between target proteins.

Language: Английский

Citations

18
Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets DOI
Alia Mushtaq, Peng Wu, Muhammad Moazzam Naseer

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 254, P. 108579 - 108579

Published: Dec. 30, 2023

Language: Английский

Citations

17
Synthesis, toxicological and in silico evaluation of novel spiro pyrimidines against Culex pipiens L. referring to chitinase enzyme DOI Creative Commons
Eslam M. Abbass, Ali Kh. Khalil, Ahmed F. El‐Farargy

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 17, 2024

Abstract The exponential development of resistance to conventional chemical insecticides adds another important motive for the creation novel insecticidal active agents. One keys meeting this challenge is exploration classes molecules with different modes action. Herein, a series spiro pyrimidine derivatives was prepared using some green synthetic methodologies such as microwave irradiation, and sonication under ultrasound waves. Spiro aminonitrile 1 key starting material synthesis targets 2–9 by reaction carbon electrophiles nitrogen nucleophiles. structures all newly synthesized compounds were approved spectral data. toxicological efficiency biological impacts assessed against Culex pipiens L. larvae. toxicity showed remarkable variations C. Where, 3 , 4 2 most efficient LC 50 values 12.43, 16.29 21.73 µg/mL, respectively. While least potent compound an value 95.18 µg/mL. As well, other arranged according follows 5 > 7 6 9 8 . In addition, exhibited significant prolongation developmental duration greatly inhibited adult emergence. Moreover, many morphological deformities observed in stages. Furthermore, cytotoxicity effective normal human cells (WI-38) non-target organisms, where weak non-toxic effects. study binding affinity correlation between structure reactivity carried out molecular docking DFT calculations investigate their mode This shed light on promising larvicidal activity life cycle.

Language: Английский

Citations

8
Synthesis, Characterizations, and Quantum Chemical Investigations on Imidazo[1,2-a]pyrimidine-Schiff Base Derivative: (E)-2-Phenyl-N-(thiophen-2-ylmethylene)imidazo[1,2-a]pyrimidin-3-amine DOI Creative Commons
Mohamed Azzouzi, Omar Azougagh,

Abderrahim Ait Ouchaoui

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 9(1), P. 837 - 857

Published: Dec. 15, 2023

In this study, (E)-2-phenyl-N-(thiophen-2-ylmethylene)imidazo[1,2-a]pyrimidin-3-amine (3) is synthesized, and detailed spectral characterizations using 1H NMR, 13C mass, Fourier transform infrared (FT-IR) spectroscopy were performed. The optimized geometry was computed the density functional theory method at B3LYP/6-311++G(d,p) basis set. theoretical FT-IR NMR (1H 13C) analysis are agreed to validate structural assignment made for (3). Frontier molecular orbitals, electrostatic potential, Mulliken atomic charge, electron localization function, localized orbital locator, natural bond orbital, nonlinear optical, Fukui functions, quantum of atoms in molecules analyses undertaken meticulously interpreted, providing profound insights into nature behaviors. addition, ADMET drug-likeness studies carried out investigated. Furthermore, docking dynamics simulations have been studied, indicating that an ideal molecule develop as a potential vascular endothelial growth factor receptor-2 inhibitor.

Language: Английский

Citations

16
Pyrazole, Pyrazoline, and Fused Pyrazole Derivatives: New Horizons in EGFR‐Targeted Anticancer Agents DOI
Ketan R Hosamani, K. Hemalatha, Rohit Pal

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(11)

Published: July 26, 2024

Pyrazole and its derivatives remain popular heterocycles in drug research, design, development. Several drugs include the pyrazole scaffold, such as ramifenazone, ibipinabant, antipyrine, axitinib, etc. They have been extensively studied by scientific community are said to a wide range of biological activity, especially anticancer agents targeting EGFR. Overexpression EGFR signalling promotes tumor growth inhibiting apoptosis. dysfunction has described multiple cancers, including colon, head neck, NSCLC, liver, breast, ovarian cancer. As result, represents prospective target for cancer treatment. anti-EGFR thriving, notably dacomitinib, afatinib, erlotinib, gefitinib, osimertinib. However, almost all currently available limited therapeutic effectiveness due lack selectivity well substantial side effects. Furthermore, aberrant across numerous human malignancies/carcinomas is impeded gene amplification, protein overexpression, mutations, or in-frame deletions, making EGFR-induced treatment challenging. To overcome such, novel with high efficacy minimal toxicity required. battle resistance inhibitors, pyrazole, pyrazoline, their investigated viable pharmacophore development new better potency, lesser toxicity, favourable pharmacokinetic characteristics. The present investigation covers examination progress toward anti-cancer therapies via fused pyrazole-based compounds. current study also inclusive data on marketed candidates undergoing preclinical clinical Lastly, we discussed recent advances medicinal chemistry significance eradication various cancers provide direction structure-activity relationship (SAR), mechanistic studies.

Language: Английский

Citations

5
Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods DOI

Nusrath Yasmeen,

Anis Ahmad Chaudhary,

Salauddin Khan

et al.

Molecular Diversity, Journal Year: 2024, Volume and Issue: 29(1), P. 215 - 239

Published: April 28, 2024

Language: Английский

Citations

4
Exploring chromone‐2‐carboxamide derivatives for triple‐negative breast cancer targeting EGFR, FGFR3, and VEGF pathways: Design, synthesis, and preclinical insights DOI
Dalia S. El‐Gamil, Mohamed Y. Zaky, Patrick M. Maximous

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(5)

Published: July 1, 2024

Chromone-based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone-2-carboxamide derivatives were synthesized evaluated for their in vitro anticancer activity against 15 human lines. Among the tested lines, MDA-MB-231, triple-negative breast line, was found to be most sensitive, where N-(2-furylmethylene) (15) α-methylated N-benzyl (17) demonstrated highest growth inhibition with GI

Language: Английский

Citations

4