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基于硫化汞的金属药物制剂作为治疗病毒和多药耐药(MDR)细菌感染的替代疗法。

Mercuric-sulphide based metallopharmaceutical formulation as an alternative therapeutic to combat viral and multidrug-resistant (MDR) bacterial infections.

机构信息

Pharmaceutical Technology Laboratory (#214, ASK-II), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, 613401, India.

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland.

出版信息

Sci Rep. 2023 Oct 4;13(1):16706. doi: 10.1038/s41598-023-43103-z.

DOI:10.1038/s41598-023-43103-z
PMID:37794044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10550948/
Abstract

According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, antibiotic resistance escalates more challenges in treatment against communicable diseases worldwide. Henceforth, the use of combinational antimicrobial therapy and metal-conjugated phytoconstituents composites are considered as alternatives. The present study explored the efficacy of mercuric-sulfide-based metallopharmaceutical, Sivanar Amirtham for anti-bacterial, anti-tuberculosis, anti-HIV therapeutics and toxicity profile by haemolytic assay, first of its kind. The anti-bacterial study was performed against both gram-positive and gram-negative pathogens including Staphylococcus aureus (ATCC 29213), Methicillin-resistant Staphylococcus aureus (MRSA: ATCC 43300), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (PA14) and Vibrio cholerae (MTCC 3905) by agar well diffusion assay, wherein the highest zone of inhibition was identified for MRSA (20.7 mm) and V. cholerae (34.3 mm) at 25 mg/mL. Furthermore, the anti-tuberculosis activity experimented by microtitre alamar blue assay against M. tuberculosis (ATCC 27294) demonstrated significant activity at the concentration range of 12.5-100 µg/mL. Additionally, the anti-HIV efficacy established by the syncytia inhibition method using C8166 cell lines infected with HIV-1, showed a significant therapeutic effect. The in-vitro toxicity assay proved Sivanar Amirtham to be non-haemolytic and haemocompatible. The physicochemical characterization studies revealed the nano-sized particles with different functional groups and the distinctive metal-mineral complex could be attributed to the multi-site targeting ability. The rationale evidence and scientific validation for the efficacy of Sivanar Amirtham ensures that it could be proposed as an alternative or adjuvant for both prophylactics and therapeutics to overcome HIV infection and antimicrobial resistance as well as the multi-drug resistance challenges.

摘要

根据全球抗菌药物耐药性和使用监测系统(GLASS)的数据,抗生素耐药性在全球范围内对传染病的治疗提出了更多挑战。因此,联合使用抗菌疗法和金属缀合植物成分复合材料被认为是替代方法。本研究通过溶血试验首次探索了基于硫化汞的金属药物 Sivanar Amirtham 的抗细菌、抗结核、抗 HIV 治疗功效和毒性特征。抗细菌研究针对包括金黄色葡萄球菌(ATCC 29213)、耐甲氧西林金黄色葡萄球菌(MRSA:ATCC 43300)、粪肠球菌(ATCC 29212)、铜绿假单胞菌(PA14)和霍乱弧菌(MTCC 3905)在内的革兰氏阳性和革兰氏阴性病原体进行了琼脂孔扩散试验,其中在 25 mg/mL 时,对 MRSA(20.7 毫米)和 V. cholerae(34.3 毫米)的抑制带最大。此外,通过微量肉汤alamar 蓝试验对结核分枝杆菌(ATCC 27294)进行的抗结核活性实验表明,在 12.5-100μg/mL 的浓度范围内具有显著活性。此外,通过使用感染 HIV-1 的 C8166 细胞系的合胞体抑制法测定的抗 HIV 功效表明具有显著的治疗效果。体外毒性试验证明 Sivanar Amirtham 是非溶血和血液相容的。物理化学特性研究表明,该药物具有不同的功能基团和独特的金属矿物复合物的纳米级颗粒,这可能归因于多部位靶向能力。Sivanar Amirtham 功效的合理证据和科学验证确保它可以作为预防和治疗的替代或辅助手段,以克服 HIV 感染和抗菌药物耐药性以及多药耐药性挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3b0/10550948/3c20d994f091/41598_2023_43103_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3b0/10550948/3c20d994f091/41598_2023_43103_Fig7_HTML.jpg
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