Synthesis of Quinoline‐Thiazolidine‐2,4‐dione Coupled Pyrazoles as in vitro EGFR Targeting Anti‐Breast Cancer Agents and Their in silico Studies

Bangaru, Mallikarjuna; Nukala, Satheesh Kumar; Kannekanti, Praveen kumar; Narsimha, Sirassu; Manchal, Ravinder; Thirukovela, Narasimha Swamy

doi:10.1002/slct.202204414

Cited by 7 publications

(1 citation statement)

References 54 publications

(78 reference statements)

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“…It has been discovered that thiazolidine‐2,4‐diones (TZDs), a family of heterocyclic compounds, may be used as cancer therapy scaffolds [10,11] . TZDs have been demonstrated to have anticancer effects through the modulation of the dynamics of the cell cycle, promoting apoptosis and cell differentiation, and inhibiting tumor angiogenesis in a variety of experimental cancer models [12,13] .…”

Section: Introductionmentioning

confidence: 99%

Novel Thiazolidine‐2,4‐Dione Derivatives as Potential VEGFR‐2 Inhibitors: Synthesis, Biological Testing, and in Silico Studies

Eissa,

Elkady,

Taghour

et al. 2024

ChemistrySelect

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In this work novel 2,4‐dioxothiazolidine‐derived compounds targeting VEGFR‐2 were designed and synthesized. Such compounds were evaluated for their anti‐proliferative and VEGFR‐2 inhibitory abilities. Compound 17 specifically demonstrated the strongest anti‐proliferative activity against the HCT‐116 cell line, with an IC50 value of 10.09 μM. Additionally, compounds 15, 18, and 19 revealed good anti‐proliferative effects with IC50 values of 12.46, 16.87, and 12.35 μM, respectively. Compound 17 demonstrated potent anti‐VEGFR‐2 efficacy, with an IC50 value of 0.068 μM, which was comparable to sorafenib (IC50 value of 0.058 μM). Compound 17 induced apoptosis in HCT‐116 cancer cells and caused G0‐G1 phase cell cycle arrest. Furthermore, it upregulated BAX levels (5.1‐fold) and downregulated Bcl‐2 levels (4.2‐fold), indicating its pro‐apoptotic effects. Compound 17 also increased caspase‐8 and caspase‐9 levels by 3.3‐fold and 4.7‐fold, respectively, compared to the control. The computational studies provided insights into the kinetic, structural properties, and binding mode of the VEGFR‐2‐17 complex. The DFT calculations elucidated compound 17′s structural and electronic properties, while computational ADMET and toxicity tests suggested acceptable degrees of drug‐likeness potential for the synthesized compounds. Our findings suggest that compound 17 holds promise as a potent apoptotic VEGFR‐2 inhibitor and may guide future efforts in developing new anticancer drugs.

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Section: Introductionmentioning

confidence: 99%

Novel Thiazolidine‐2,4‐Dione Derivatives as Potential VEGFR‐2 Inhibitors: Synthesis, Biological Testing, and in Silico Studies

Eissa,

Elkady,

Taghour

et al. 2024

ChemistrySelect

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Current scenario of pyrazole hybrids with anti‐breast cancer therapeutic applications

2024

Archiv der Pharmazie

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Breast cancer stands as the leading cause of cancer‐related deaths among women globally, but current therapy is restricted to the serious adverse effects and multidrug resistance, necessitating the exploration of novel, safe, and efficient anti‐breast cancer chemotherapeutic agents. Pyrazoles exhibit excellent potential for utilization as effective anti‐breast cancer agents due to their ability to act on various biological targets. Particularly, pyrazole hybrids demonstrated the advantage of targeting multiple pathways, and some of them, which are exemplified by larotrectinib (pyrazolo[1,5‐a]pyrimidine hybrid), can be applied for breast cancer therapy. Thus, pyrazole hybrids hold great promise as useful therapeutic interventions for breast cancer. The aim of this review is to summarize the current scenario of pyrazole hybrids with in vitro and/or in vivo anti‐breast cancer potential, along with the modes of action and structure–activity relationships, covering articles published from 2020 to the present, to streamline the development of rational, effective and safe anti‐breast cancer candidates.

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Fused Imidazo[1,2‐d][1,2,4]Thiadiazolo[1,2,3]Triazoles: One‐Pot Synthesis, Anti‐Bacterial, Anti‐Biofilm and TLR4 Inhibitory Activities

Premalatha,

Azam,

Kapavarapu

et al. 2024

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We developed and evaluated several new fused imidazo[1,2‐d][1,2,4]thiadiazolo[1,2,3]triazoles to see how they perform against bacteria and biofilms. Some compounds showed acceptable activity compared to the primary standard, Dicloxacillin. Some of the compounds demonstrated significant antibacterial activity against S. aureus, with MIC values ranging from 1.56–12.5 μg/mL. We also found anti‐biofilm properties in the potent compounds. The results showed that derivatives 3‐(4‐fluorophenyl)imidazo[1,2‐d] [1,2,3] triazolo[1,5‐b][1,2,4]thiadiazole 8,8‐dioxide and 3‐(3,5‐difluorophenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide were strong antibacterial agents and effective MSSA and MRSA biofilm growth inhibitors. We conducted in silico studies to assess the molecular interactions of more potent compounds with TLR4 proteins (PDB: 3FXI, 3VQ1, 3RG1). Our findings revealed that 3‐(4‐chloro‐3,5‐dimethoxyphenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b] [1,2,4]thiadiazole 8,8‐dioxide, 3‐(3,5‐dichlorophenyl)imidazo[1,2‐d] [1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide, and 3‐(4‐(trifluoromethyl)phenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide exhibited more binding interactions than dicloxacillin. ADME of more potent compounds examined in this study and compounds could potentially inhibit the cytochrome P450 CYP2C19 isoform.

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Synthesis of Quinoline‐Thiazolidine‐2,4‐dione Coupled Pyrazoles as in vitro EGFR Targeting Anti‐Breast Cancer Agents and Their in silico Studies

Cited by 7 publications

References 54 publications

Novel Thiazolidine‐2,4‐Dione Derivatives as Potential VEGFR‐2 Inhibitors: Synthesis, Biological Testing, and in Silico Studies

Novel Thiazolidine‐2,4‐Dione Derivatives as Potential VEGFR‐2 Inhibitors: Synthesis, Biological Testing, and in Silico Studies

Current scenario of pyrazole hybrids with anti‐breast cancer therapeutic applications

Fused Imidazo[1,2‐d][1,2,4]Thiadiazolo[1,2,3]Triazoles: One‐Pot Synthesis, Anti‐Bacterial, Anti‐Biofilm and TLR4 Inhibitory Activities

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