Gaddaguti Venugopal, Venkateswara Rao Talluri, Prasada Rao Allu
Department of Biotechnology, KL University, Vaddeswaram, Guntur, AP, 522 502, India.
Department of Horticulture, Sikkim University, Samdur, Tadong, Gangtok, Sikkim, 737 102, India.
3 Biotech. 2016 Jun;6(1):26. doi: 10.1007/s13205-015-0346-x. Epub 2016 Jan 11.
Mosquitoes are exceptionally efficient in detecting their hosts for blood meal using odorant binding proteins, viz. 3N7H and 3Q8I and spread several dreadful diseases. DEET is a synthetic mosquito repellent widely used all over world for protection against mosquito bite. Reports reveal that, synthetic mosquito repellents may pose health problems in considerably large population. In view of the above fact, we made an attempt to discover efficient and novel natural mosquito repellent compounds with least impact on human health. Methanolic leaf extracts of Ocimum basilicum Linn. var. pilosum (willd.)-Benth and Ocimum tenuiflorum var. CIM-AYU were subjected to GC-MS analysis and obtained 35 phytochemical constituents. Repellent potentiality of the Ocimum compounds was assessed against 3Q8I and 3N7H of Anopheles gambiae. PDB structures of mosquito odorant binding proteins were downloaded, processed and docking studies were performed along with reference ligand DEET using Schrodinger MAESTRO 9.2 software. Molecular docking results reveal that phenol, 2-methoxy-3-(2-propenyl)-, licopersin, gamma sitosterol and benzene, 1,2-dimethoxy-4-(2-propenyl)- from O. tenuiflorum var. CIM-AYU are strongly bound with 3N7H. Whereas, 4h-1-benzopyran-4-one, 5-hydroxy-6,7-dimethoxy-2-(4-methoxyphenyl)-, catechol and monoacetin from O. basilicum Linn. var. pilosum (willd.)-Benth. show high binding affinity with odorant binding protein 3Q8I. All natural compounds tested in the present study display better docking scores than DEET. The results further substantiate that the 12 out of 35 compounds of the two Ocimum species found to be ideal candidates for design and development of potential mosquito repellents. ADME properties of the tested compounds further confirm that bioactive compounds of Ocimum species were found to be in acceptable range. Synchronized application of at least two different natural compounds (with best docking scores) which target 3N7H and 3Q8I (Odorant Binding Proteins of mosquito) proteins may provide enhanced protection against mosquitoes bite. Based on the ADME properties, natural compounds of Ocimum species can be considered for design and development of safe mosquito repellents.
蚊子利用气味结合蛋白（即3N7H和3Q8I）来极其高效地探测宿主以获取血餐，并传播多种可怕的疾病。避蚊胺是一种合成驱蚊剂，在全球广泛使用以防止蚊虫叮咬。报告显示，合成驱蚊剂可能会给相当多的人群带来健康问题。鉴于上述事实，我们试图发现对人类健康影响最小的高效新型天然驱蚊化合物。对罗勒叶（Ocimum basilicum Linn. var. pilosum (willd.)-Benth）和圣罗勒（Ocimum tenuiflorum var. CIM-AYU）的甲醇叶提取物进行了气相色谱-质谱分析，得到了35种植物化学成分。评估了罗勒属化合物对冈比亚按蚊的3Q8I和3N7H的驱避潜力。下载了蚊子气味结合蛋白的PDB结构，进行了处理，并使用Schrodinger MAESTRO 9.2软件与参考配体避蚊胺一起进行了对接研究。分子对接结果表明，圣罗勒（Ocimum tenuiflorum var. CIM-AYU）中的2-甲氧基-3-(2-丙烯基)苯酚、番茄红素、γ-谷甾醇和1,2-二甲氧基-4-(2-丙烯基)苯与3N7H紧密结合。而罗勒叶（Ocimum basilicum Linn. var. pilosum (willd.)-Benth）中的5-羟基-6,7-二甲氧基-2-(4-甲氧基苯基)-4H-1-苯并吡喃-4-酮、儿茶酚和甘油单乙酸酯与气味结合蛋白3Q8I表现出高结合亲和力。本研究中测试的所有天然化合物的对接分数均优于避蚊胺。结果进一步证实，这两种罗勒属植物的35种化合物中有12种被发现是设计和开发潜在驱蚊剂的理想候选物。测试化合物的药代动力学性质进一步证实，罗勒属植物的生物活性化合物处于可接受范围内。同时应用至少两种针对3N7H和3Q8I（蚊子的气味结合蛋白）的不同天然化合物（对接分数最佳）可能会增强对蚊虫叮咬的防护。基于药代动力学性质，罗勒属植物的天然化合物可考虑用于设计和开发安全的驱蚊剂。
