Kumar Puneet, Saini Sapna, Gangwar Anjali, Sharma Rashmi, Anal Jasha Momo H
Natural Products and Medicinal Chemistry Division, CSIR- Indian Institute of Integrative Medicine Jammu 180001 India
Academy of Scientific and Innovative Research (AcSIR) Ghaziabad 201002 India.
RSC Adv. 2024 Oct 17;14(45):32771-32785. doi: 10.1039/d4ra05370b.
Isobavachalcone (IBC) is a natural prenylated flavonoid containing chalcone and prenyl chain moieties with a wide range of biological and pharmacological properties. In this work, we synthesized structurally diversified derivatives (IBC-2 to IBC-10) from the natural prenylated chalcone IBC isolated from and assessed their antibacterial potency against the Gram-positive and Gram-negative bacterial strains ATCC 29213, ATCC 15187, ATCC25922 and ATCC 27853. IBC and IBC-2 exhibited a minimum inhibition concentration (MIC) of 5.0 μM against ATCC 29213, whereas IBC-3 exhibited a broad-spectrum activity against Gram-positive and Gram-negative pathogens. Cytotoxicity assessments on the murine RAW 264.7 macrophage cell line revealed minimal to moderate cytotoxicity for IBC-2 and IBC-3 with a favorable selectivity index (>10). Time- and concentration-dependent studies further supported the bactericidal nature of the compounds, as IBC, IBC-2, and IBC-3 exhibited concentration-dependent killing of in a time-dependent manner. Furthermore, combination studies, SEM analysis, and PI staining suggest that IBC-3's mechanism of action targets the bacteria's cytoplasmic membrane or cell wall. The bioactive compounds displayed promising drug-like characteristics and a favorable pharmacokinetic profile (ADME-Tox), indicating a projected high oral bioavailability. Structure-activity relationships (SARs) drawn from this study reveal that a prenyl chain at the A-ring and hydroxy functional groups attached to the aromatic rings of chalcone scaffolds are responsible for this antibacterial potential, which will be helpful in the future discovery and development of antibiotics from natural products to overcome the antibiotic resistance crisis.
异补骨脂查耳酮（IBC）是一种天然的异戊烯基黄酮，含有查耳酮和异戊烯基链部分，具有广泛的生物学和药理学特性。在这项工作中，我们从从[具体来源未给出]分离得到的天然异戊烯基查耳酮IBC合成了结构多样的衍生物（IBC - 2至IBC - 10），并评估了它们对革兰氏阳性和革兰氏阴性细菌菌株ATCC 29213、ATCC 15187、ATCC25922和ATCC 27853的抗菌效力。IBC和IBC - 2对ATCC 29213表现出5.0 μM的最低抑菌浓度（MIC），而IBC - 3对革兰氏阳性和革兰氏阴性病原体表现出广谱活性。对小鼠RAW 264.7巨噬细胞系的细胞毒性评估显示，IBC - 2和IBC - 3具有最小至中度的细胞毒性，且选择性指数良好（>10）。时间和浓度依赖性研究进一步支持了这些化合物的杀菌性质，因为IBC、IBC - 2和IBC - 3以时间依赖性方式表现出对[具体细菌未给出]的浓度依赖性杀伤作用。此外，联合研究、扫描电子显微镜（SEM）分析和碘化丙啶（PI）染色表明，IBC - 3的作用机制靶向细菌的细胞质膜或细胞壁。这些生物活性化合物表现出有前景的类药物特性和良好的药代动力学特征（ADME - Tox），表明预计具有高口服生物利用度。从这项研究得出的构效关系（SARs）表明，A环上的异戊烯基链和连接在查耳酮支架芳香环上的羟基官能团是这种抗菌潜力的原因，这将有助于未来从天然产物中发现和开发抗生素以克服抗生素耐药性危机。
