"Targeting Detoxifying Enzymes in the Lymphatic Filariasis Vector: An I" by Rizal Subahar, Rawina Winita et al.
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Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

Vector control remains a critical component in the prevention of lymphatic filariasis, a disease transmitted by insect vectors. Natural compounds such as curcumin, camphor, and menthol are being explored for their bio-insecticidal properties due to their potential to inhibit key detoxification and neurological enzymes in insects, including acetylcholinesterase (AChE), glutathione S-transferase (GST), and cytochrome P450 oxidases (CYP450). A molecular docking study using SwissDock was conducted to evaluate the interaction of curcumin, camphor, and menthol with AChE, GST, and CYP450 enzymes. Binding affinity (ΔG), hydrogen bonding, and active site interactions were analyzed to assess the inhibitory potential of each compound. Curcumin showed the highest binding affinity across all target enzymes. AChE (-8.2 kcal/mol), GST (-7.9 kcal/mol), and CYP450 (-7.5 kcal/mol). It formed strong hydrogen bonds with key catalytic residues, suggesting effective inhibition of neurotoxicity and detoxification pathways. Camphor displayed moderate binding affinities with AChE (-7.1 kcal/mol), GST (-6.5 kcal/mol), and CYP450 (-7.2 kcal/mol), primarily through hydrophobic interactions. Menthol exhibited the weakest binding, with limited hydrogen bonding and lower affinities (AChE: -6.4 kcal/mol, GST:-5.9 kcal/mol, CYP450: -6.3 kcal/mol). The findings suggest that curcumin is a promising candidate for insect vector control through inhibition of critical enzyme systems involved in neurotransmission and detoxification. Camphor may offer moderate bioactivity, while menthol appears less potent. These insights support further exploration of phenolic compounds as environmentally friendly, natural insecticidal agents against vectors of lymphatic filariasis.

Bahasa Abstract

Pengendalian vektor tetap menjadi komponen penting dalam pencegahan filariasis limfatik, penyakit yang ditularkan oleh vektor serangga. Senyawa alami seperti kurkumin, camphor dan mentol sedang dieksplorasi untuk sifat bioinsektisidalnya karena potensinya untuk menghambat enzim detoksifikasi dan neurologis kunci pada serangga, termasuk asetilkolinesterase (AChE), glutation S-transferase (GST), dan sitokrom P450 oksidase (CYP450). Sebuah studi docking molekuler menggunakan SwissDock dilakukan untuk mengevaluasi interaksi kurkumin, camphor, dan mentol dengan enzim AChE, GST, dan CYP450. Afinitas pengikatan (ΔG), ikatan hidrogen, dan interaksi situs aktif dianalisis untuk menilai potensi penghambatan masing-masing senyawa. Kurkumin menunjukkan afinitas pengikatan tertinggi di antara semua enzim target. AChE (-8,2 kcal/mol), GST (-7,9 kcal/mol), dan CYP450 (-7,5 kcal/mol) yang membentuk ikatan hidrogen yang kuat dengan residu katalitik kunci, menunjukkan penghambatan yang efektif terhadap neurotoksisitas dan jalur detoksifikasi. Kamfer menunjukkan afinitas pengikatan sedang dengan AChE (-7,1 kcal/mol), GST (-6,5 kcal/mol), dan CYP450 (-7,2 kcal/mol), terutama melalui interaksi hidrofobik. Menthol menunjukkan ikatan terlemah, dengan ikatan hidrogen yang terbatas dan afinitas yang lebih rendah (AChE: -6,4 kcal/mol, GST: -5,9 kcal/mol, CYP450: -6,3 kcal/mol). Temuan tersebut menunjukkan bahwa kurkumin adalah kandidat yang menjanjikan untuk pengendalian vektor serangga melalui penghambatan sistem enzim kritis yang terlibat dalam neurotransmisi dan detoksifikasi. Camphor mungkin menawarkan bioaktivitas sedang, sementara mentol tampak kurang kuat. Wawasan ini mendukung eksplorasi lebih lanjut terhadap senyawa fenolik sebagai agen insektisida alami yang ramah lingkungan terhadap vektor filariasis limfatik.

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