Kumar Saurabh, Mina Pooja Rani, Kumar Ravi, Pal Anirban, Ahmad Ateeque, Tandon Sudeep, Darokar Mahendra P
Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
Process Chemistry and Technology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
Front Pharmacol. 2021 Mar 10;12:628970. doi: 10.3389/fphar.2021.628970. eCollection 2021.
Malaria remains one of the major health concerns due to the resistance of species toward the existing drugs warranting an urgent need for new antimalarials. Thymol derivatives were known to exhibit enhanced antimicrobial activities; however, no reports were found against spp. In the present study, the antiplasmodial activity of thymol derivatives was evaluated against chloroquine-sensitive (NF-54) and -resistant (K1) strains of . Among the thymol derivatives tested, 4-chlorothymol showed potential activity against sensitive and resistant strains of . 4-Chlorothymol was found to increase the reactive oxygen species and reactive nitrogen species level. Furthermore, 4-chlorothymol could perturb the redox balance by modulating the enzyme activity of GST and GR. 4-Chlorothymol also showed synergy with chloroquine against chloroquine-resistant . 4-Chlorothymol was found to significantly suppress the parasitemia and increase the mean survival time in assays. Interestingly, in assay, 4-chlorothymol in combination with chloroquine showed higher chemosuppression as well as enhanced mean survival time at a much lower concentration as compared to individual doses of chloroquine and 4-chlorothymol. These observations clearly indicate the potential use of 4-chlorothymol as an antimalarial agent, which may also be effective in combination with the existing antiplasmodial drugs against chloroquine-resistant infection. cytotoxicity/hemolytic assay evidently suggests that 4-chlorothymol is safe for further exploration of its therapeutic properties.
疟疾仍然是主要的健康问题之一，因为疟原虫物种对现有药物产生耐药性，迫切需要新的抗疟药物。已知百里酚衍生物具有增强的抗菌活性；然而，尚未发现针对疟原虫属的相关报道。在本研究中，评估了百里酚衍生物对氯喹敏感（NF - 54）和耐药（K1）疟原虫菌株的抗疟活性。在所测试的百里酚衍生物中，4 - 氯百里酚对疟原虫的敏感和耐药菌株均显示出潜在活性。发现4 - 氯百里酚可增加活性氧和活性氮水平。此外，4 - 氯百里酚可通过调节谷胱甘肽S - 转移酶（GST）和谷胱甘肽还原酶（GR）的酶活性来扰乱氧化还原平衡。4 - 氯百里酚与氯喹联合使用时，对氯喹耐药的疟原虫也显示出协同作用。在实验中发现4 -氯百里酚可显著抑制疟原虫血症并延长平均存活时间。有趣的是，在实验中，与氯喹和4 - 氯百里酚的单独剂量相比，4 - 氯百里酚与氯喹联合使用时，在低得多的浓度下就显示出更高的化学抑制作用以及更长的平均存活时间。这些观察结果清楚地表明4 - 氯百里酚作为抗疟药物的潜在用途，它与现有的抗疟药物联合使用时，可能对氯喹耐药的疟原虫感染也有效。细胞毒性/溶血试验明显表明4 - 氯百里酚对于进一步探索其治疗特性是安全的。
