Reza Zadali1, Samad Nejad Ebrahimi2, Zahra Tofighi1, Ali Es-Haghi3, Matthias Hamburger4, Marcel Kaiser5,6, Massimiliano D' Ambola7, Nunziatina De Tommasi7, Abbas Hadjiakhoondi8,9. 1. Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University G. C., Evin, Tehran, Iran. s_ebrahimi@sbu.ac.ir. 3. Department of Physico Chemistry, Razi Vaccine & Serum Research Institute (RVSRI), Karaj, Iran. 4. Pharmaceutical Biology, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland. 5. Swiss Tropical and Public Health Institute, Swiss Tropical Institute, Socinstrasse 57, 4051, Basel, Switzerland. 6. University of Basel, Petersplatz 1, 4003, Basel, Switzerland. 7. Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy. 8. Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. abbhadji@tums.ac.ir. 9. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. abbhadji@tums.ac.ir.
Abstract
PURPOSE: Zhumeria majdae, a unique species of the Zhumeria genus, is an endemic Iranian plant in the Lamiaceae family. Phytochemical investigation and biological activity of this plant are rarely reported. The current study aimed to find new antiprotozoal compounds from the roots of Z. majdae and to determine the absolute configuration of isolated compounds by circular dichroism. METHODS: The extraction process from roots and aerial parts of Z. majdae was carried out by hexane, ethyl acetate and methanol followed by testing their antiprotozoal effects against Leishmania donovani, Trypanosoma brucei rhodesiense, T. cruzi, and Plasmodium falciparum, respectively. Structure elucidation was done using 1D and 2D NMR spectroscopy and HREIMS spectrometry. In addition, experimental and theoretical circular dichroism spectroscopy was used to establish absolute configuration. RESULTS: In comparison with aerial parts, the hexane extract from roots showed superior activity against T. b. rhodesiense, L. donovani and P. falciparum with IC50 values of 5.4, 1.6 and 2.1 μg/ml, respectively. From eight abietane-type diterpenoids identified in roots, six were reported for the first time in the genus Zhumeria. 11,14-dihydroxy-8,11,13-abietatrien-7-one (6) exhibited a promising biological activity against P. falciparum (IC50 8.65 μM), with a selectivity index (SI) of 4.6, and lanugon Q (8) showed an IC50 value of 0.13 μM and SI of 15.4 against T. b. rhodesiense. CONCLUSION: Altogether, according to the results, of 8 isolated compounds, dihydroxy-8,11,13-abietatrien-7-one (6) and lanugon Q (8) exhibited a promising activity against T. b. rhodesiense and P. falciparum. In conclusion, these compounds could be potential candidates for further analysis and may serve as lead compounds for the synthesis of antiprotozoal agents. Graphical abstract.
PURPOSE:Zhumeria majdae, a unique species of the Zhumeria genus, is an endemic Iranian plant in the Lamiaceae family. Phytochemical investigation and biological activity of this plant are rarely reported. The current study aimed to find new antiprotozoal compounds from the roots of Z. majdae and to determine the absolute configuration of isolated compounds by circular dichroism. METHODS: The extraction process from roots and aerial parts of Z. majdae was carried out by hexane, ethyl acetate and methanol followed by testing their antiprotozoal effects against Leishmania donovani, Trypanosoma brucei rhodesiense, T. cruzi, and Plasmodium falciparum, respectively. Structure elucidation was done using 1D and 2D NMR spectroscopy and HREIMS spectrometry. In addition, experimental and theoretical circular dichroism spectroscopy was used to establish absolute configuration. RESULTS: In comparison with aerial parts, the hexane extract from roots showed superior activity against T. b. rhodesiense, L. donovani and P. falciparum with IC50 values of 5.4, 1.6 and 2.1 μg/ml, respectively. From eight abietane-type diterpenoids identified in roots, six were reported for the first time in the genus Zhumeria. 11,14-dihydroxy-8,11,13-abietatrien-7-one (6) exhibited a promising biological activity against P. falciparum (IC50 8.65 μM), with a selectivity index (SI) of 4.6, and lanugon Q (8) showed an IC50 value of 0.13 μM and SI of 15.4 against T. b. rhodesiense. CONCLUSION: Altogether, according to the results, of 8 isolated compounds, dihydroxy-8,11,13-abietatrien-7-one (6) and lanugon Q (8) exhibited a promising activity against T. b. rhodesiense and P. falciparum. In conclusion, these compounds could be potential candidates for further analysis and may serve as lead compounds for the synthesis of antiprotozoal agents. Graphical abstract.