Design and synthesis of novel tetrabromophthalimide derivatives as potential tubulin inhibitors endowed with apoptotic induction for cancer treatment

Drug Development Research, Год журнала: 2024, Номер 85(4)

Опубликована: Май 15, 2024

Abstract Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as vital component cellular skeleton, playing pivotal process cell division making it an attractive target cancer treatment. Hence, scope work was adapted design and synthesize new anti‐tubulin tetrabromophthalimide hybrids ( 3 ‐ 17 ) with colchicine binding site (CBS) inhibitory potential. The conducted vitro studies showed that compound 16 displayed lowest IC 50 values (11.46 µM) at FaDu lines, whereas exhibited value (13.62 PC3 line. However, 7b (11.45 MDA‐MB‐468 Moreover, observed be superior antitumor candidate against all three tested lines (MDA‐MB‐468, PC3, FaDu) 17.22, 13.15, 13.62 µM, respectively. In addition, well‐established upregulation apoptotic markers (Caspases 3, 7, 8, 9, Bax, P53). induced downregulation antiapoptotic (MMP2, MMP9, BCL‐2). Furthermore, inhibition assay compounds 15a particularly significant potentials, 23.07 4.25 respectively, compared colchicine, which had 3.89 µM. Additionally, cycle analysis conducted, showing could prompt arrest both G0‐G1 G2‐M phases. On other hand, molecular docking approach applied investigate interactions examined candidates towards CBS β‐tubulin subunit. Thus, synthesized can regarded outstanding anticancer activity.

Язык: Английский

---

Azole Derivatives: Cutting‐Edge Agents in Cancer Therapy

ChemistrySelect, Год журнала: 2024, Номер 9(43)

Опубликована: Ноя. 1, 2024

Abstract Monocyclic 5‐membered heterocycles including imidazoles, thiazoles, oxazoles, and their related compounds have gained significant attention in medicinal chemistry because of potent anticancerous activity. These small heterocyclic molecules possess versatile properties, biological activity, absorption, distribution, metabolism, excretion, chemical diversity that give them immense potential as anticancer agents. It is also a fact inherent characteristic azoles to combine with many through hydrogen bond, stacking, hydrophobic interaction makes effective against almost all cancer types. In the present paper author discusses way which connected structure monocyclic activity namely ability these intercalate DNA, inhibit some enzymes interfere cellular signaling pathways. Interestingly, several azole derivatives been seen be preclinical efficacy studies well clinical trials are considered overcoming problem resistance side effects common As synthetic progresses, structural system has diversified development pharmacology become more specific. This helped enhancing formation new class improved selectivity efficacy. Furthermore, comprehensive review explains how computational structure‐activity relationship (SAR) approaches applied design future‐generation compounds. light facts, this article designed broad overview current state azole‐based agents an attempt further assert its therapeutic promise spur attempts at infusing said into therapeutics fray. The discoveries made study may allow radical different approaches, could lead targeted treatment cancer.

Язык: Английский

---

Novel uracil derivatives as anti-cancer agents: Design, synthesis, biological evaluation and computational studies

Journal of Molecular Structure, Год журнала: 2023, Номер 1302, С. 137435 - 137435

Опубликована: Дек. 27, 2023

Язык: Английский

---

Exploring the Antioxidant Potency of New Naphthalene‐Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations

Chemistry & Biodiversity, Год журнала: 2023, Номер 20(12)

Опубликована: Ноя. 1, 2023

Naphthalene-based chalcone derivative was successfully synthesized through the condensation of 2,4-dichlorobenzaldehyde with 2-acetylnaphthalene. This chalcone, denoted as compound 1, demonstrated a versatile reactivity upon treatment both nitrogen and carbon nucleophiles, yielded diverse heterocyclic scaffolds such pyrazoline, thiazole, pyrimidine, pyran, pyridine derivatives. The pyrazoline aldehyde 7 further derivatized to produce hydrazide-hydrazone 13, namely, (1H-pyrazol-1-yl)methylene)acetohydrazide, which exploited synthesize derivatives 2-oxo-2H-chromene-3-carbohydrazide 14, 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetohydrazide 15, 3-(4-nitrophenyl)acrylohydrazide 16. All newly compounds were characterized by melting point, elemental analysis, well FT-IR, 1 H-NMR mass spectroscopy. Furthermore, these screened for their antioxidant capacities using DPPH radical assay. results showed that 5 10 are most potent antioxidants IC50 values 178, 177(μM), respectively. comparable ascorbic acid has value 148. Meanwhile, 2, 12, 16 exhibited moderate activities ranged from 266 291(μM). Thus, heterocycles could emerge promising drugs oxidative stress-related diseases. Finally, molecular docking conducted study binding affinity 5, 10, inside active pocket Human Peroxiredoxin (1HD2). DFT calculations global descriptors calculated correlate relation between chemical structure reactivity.

Язык: Английский

---

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

Chemistry & Biodiversity, Год журнала: 2023, Номер 21(2)

Опубликована: Дек. 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.

Язык: Английский

---