Sharma Uday Raj, Roy Sushavan, Purawargaar Matada Gurubasavaraja Swamy, P M Manjunatha, Janadri Suresh, Vada Surendra, Haribabu T, Taj Nageena, S V Gayathri, Pal Rohit, Das Susovan, Chanda Nirmal
Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, 560107, India.
Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep 10. doi: 10.1007/s00210-025-04470-8.
This study aimed to synthesize and evaluate the anticancer activity of novel chalcone derivative against colon cancer by in vitro cytotoxicity against HCT-116 (Research Resource Identifiers:CVCL_D4JB) cell line and in vivo using EAC (Research Resource Identifiers: CVCL_1306) and DLA (Research Resource Identifiers: CVCL_VR37) cells inoculated Swiss albino mice. The present study aimed to synthesize the new chalcone derivatives and conduct its anti-colon cancer activity both in vitro and in vivo. The designed compounds were subjected to in silico studies like binding pocket analysis, molecular docking, and ADME studies. The compounds were synthesized using the Claisen-Schmidt condensation technique. The synthesized compounds were then characterized using FT-IR, NMR, and MS. Further, synthesized the compounds were subjected to an in vitro cytotoxicity study using an MTT assay against the HCT-116 cell line. The therapeutic efficacy of novel chalcone derivative was evaluated against (Ehrlich Ascites Carcinoma) EAC and (Dalton's Lymphoma Ascites) DLA cell inoculated Swiss albino mice. The characterization of the compounds using FT-IR, NMR, and MS confirmed the formation of the new chalcone derivatives. One synthesized compound showed good cytotoxicity against the HCT-116 cell line with an IC50 value of 15.90 μg/ml. In the in vivo pharmacodynamic parameters, the S1 maintained stable body weight, decrease in tumour volume, and tumour weight, and increased the life span of cancer-induced mice. Haematological profiles such as RBC, WBC, Hb, and Platelet count revealed nearly normal levels in S1-treated mice in both EAC and DLA cell-inoculated mice. All the observations convey that the novel chalcone derivative (S1) has potency in dose-dependent anticancer activity comparable to 5-flurouracil.
本研究旨在通过对HCT - 116(研究资源标识符:CVCL_D4JB)细胞系进行体外细胞毒性实验以及对接种了艾氏腹水癌(EAC,研究资源标识符:CVCL_1306)和道尔顿淋巴瘤腹水(DLA,研究资源标识符:CVCL_VR37)细胞的瑞士白化小鼠进行体内实验,来合成并评估新型查尔酮衍生物对结肠癌的抗癌活性。本研究旨在合成新型查尔酮衍生物并在体外和体内进行其抗结肠癌活性研究。对设计的化合物进行了计算机模拟研究,如结合口袋分析、分子对接和药物代谢动力学研究。使用克莱森 - 施密特缩合技术合成化合物。然后使用傅里叶变换红外光谱(FT - IR)、核磁共振(NMR)和质谱(MS)对合成的化合物进行表征。此外,使用MTT法对合成的化合物针对HCT - 116细胞系进行体外细胞毒性研究。评估新型查尔酮衍生物对接种了艾氏腹水癌(EAC)和道尔顿淋巴瘤腹水(DLA)细胞的瑞士白化小鼠的治疗效果。使用FT - IR、NMR和MS对化合物进行表征证实了新型查尔酮衍生物的形成。一种合成化合物对HCT - 116细胞系显示出良好的细胞毒性,IC50值为15.90μg/ml。在体内药效学参数方面,S1使体重保持稳定,肿瘤体积和肿瘤重量减小,并延长了癌症诱导小鼠的寿命。血液学指标如红细胞(RBC)、白细胞(WBC)、血红蛋白(Hb)和血小板计数显示,在接种EAC和DLA细胞的小鼠中,经S1处理的小鼠的这些指标接近正常水平。所有观察结果表明,新型查尔酮衍生物(S1)具有与5 - 氟尿嘧啶相当的剂量依赖性抗癌活性。