Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing

Pharmaceuticals

Ghulam Abbas¹  Ajmal Khan²  Najeeb Ur Rehman²  Majid Khan²  Husain Yar Khan²  Hidayat Hussain²  Ahmed Al-Harrasi²  Kashif Rafiq²  SobiaAhsan Halim² 

[1] Department of Biological Sciences and Chemistry, University of Nizwa, P.O Box 33, 616 Birkat Al Mauz, Nizwa, Sultanate of Oman;Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, 616 Birkat Al Mauz, Nizwa, Sultanate of Oman;

关键词: Lycium shawii Roem. &;    Schult;    Aloe vera (L.) BURM. F.;    antiproliferative;    antioxidant;    pharmacophore modeling;   

DOI  :  10.3390/ph13050094

来源: DOAJ

【 摘 要 】

Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (¹H and ¹³C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC₅₀ values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC₅₀ values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC₅₀ = 14.4 µM), 12 (IC₅₀ = 23.3), and 2 (IC₅₀ = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs.

【 授权许可】

Unknown