Thiamphenicol, a methyl-sulfonyl derivative of Chloramphenicol, is a broad-spectrum antimicrobial antibiotic[1]. Thiamphenicol acts by binding to the 50S ribosomal subunit, leading to inhibition of protein synthesis and bacteriostatic effect[2]. Thiamphenicol exhibits inhibitory activity against Gram-positive bacteria, Gram-negative aerobes, and anaerobes, and is commonly employed in studies of bacterial infection mechanisms and the mode of action of antibacterial agents[3][4].
In vitro, in agar culture system, Thiamphenicol (36μg/mL; 8 or 24h) reversibly suppresses mouse bone marrow CFC proliferation and markedly reduces colony formation via inhibition of mitochondrial protein synthesis, while simultaneously skewing CFC differentiation toward macrophage colonies (97–100% versus 20–50% in controls) and reducing granulocytic colonies to<5%[5].
In vivo, Thiamphenicol (216mg/kg; i.p.) administered 1h before LPS challenge and maintained for 12h significantly decreased the lung wet-to-dry ratio in LPS-induced ALI mice, reduced neutrophil and total cell counts in bronchoalveolar lavage fluid, suppressed IL-6 and IL-1β mRNA expression in lung tissue, and reversed LPS-induced ultrastructural damage to the alveolar–capillary barrier and degradation of VE-cadherin protein[6]. Thiamphenicol (250mg/kg; subcutaneously implanted dialysis bag; 7 days) significantly reduced peripheral reticulocyte counts and caused a decline in total red blood cell numbers in normal rabbits; in phlebotomized anaemic rabbits, this dosage markedly suppressed the proliferation and differentiation of erythroid progenitor cells in the marrow, decreasing the erythroid precursor fraction from 75% to 0%, while also lowering reticulocyte haemoglobin synthesis rate and ribosomal content without affecting plasma erythropoietin levels[7].
References:
[1] Mariani L. Cloramfenicolo e tiamfenicolo [Chloramphenicol and thiamphenicol]. Clin Ter. 1978;86(3):195-218.
[2] Marchese A, Debbia EA, Tonoli E, Gualco L, Schito AM. In vitro activity of thiamphenicol against multiresistant Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Italy. J Chemother. 2002;14(6):554-561.
[3] Dinos GP, Athanassopoulos CM, Missiri DA, et al. Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions. Antibiotics (Basel). 2016;5(2):20.
[4] Raymond J, Boutros N, Bergeret M. Place du thiamphénicol dans le traitement des pneumopathies communautaires [Role of thiamphenicol in the treatment of community-acquired lung infections]. Med Trop (Mars). 2004;64(1):33-38.
[5] Ratzan RJ, Moore MA, Yunis AA. Effect of chloramphenicol and thiamphenicol on the in vitro colony-forming cell. Blood. 1974;43(3):363-369.
[6] Zhang Z , Xie J , Shan N ,et al.Discovery of the specific inhibitory effect of thiamphenicol on LPS-induced acute lung injury (ALI) in mice through virtual screening and biological evaluation.Journal of Molecular Structure. 2022, 1257:132638.
[7] Nijhof W, Wierenga PK, Kardaun S. The effect of thiamphenicol on the production of immature red blood cells under anaemic conditions. Br J Haematol. 1977;36(1):29-40.
Thiamphenicol是Chloramphenicol的甲砜基衍生物，是一种广谱抗菌抗生素[1]。Thiamphenicol通过与50S核糖体亚基结合，抑制蛋白质合成，从而发挥抑菌作用[2]。Thiamphenicol对革兰氏阳性菌、革兰氏阴性需氧菌及厌氧菌均具有抑制作用，常用于细菌感染机制及抗菌药作用模式的研究[3][4]。
体外实验中，在琼脂培养体系中，Thiamphenicol（36μg/mL；作用8或24小时）通过抑制线粒体蛋白质合成，可逆性抑制小鼠骨髓集落形成细胞（CFC）的增殖并显著减少集落形成，同时使CFC向巨噬细胞集落分化比例从20–50%升高至97–100%，粒细胞集落比例降至<5%[5]。
体内实验中，Thiamphenicol（216mg/kg；腹腔注射）于LPS刺激前1小时给药并持续12小时，可显著降低LPS诱导的急性肺损伤（ALI）小鼠肺湿干比，减少支气管肺泡灌洗液中的中性粒细胞及总细胞数，抑制肺组织IL-6和IL-1β mRNA表达，并逆转LPS引起的肺泡–毛细血管屏障超微结构损伤及VE-钙黏蛋白降解[6]。Thiamphenicol（250mg/kg；皮下植入透析袋给药；7天）在正常兔中显著减少外周血网织红细胞数量并导致红细胞总数下降；在放血性贫血兔中，该剂量显著抑制骨髓红系祖细胞的增殖与分化，使红细胞前体比例自75%降至0%，同时降低网织红细胞血红蛋白合成速率及核糖体含量，而不影响血浆促红细胞生成素水平[7]。