Bioassay-guided isolation of novel and selective urease inhibitors from Diospyros lotus

Abdur Rauf; Ghias Uddin; Bina S Siddiqui; Ajmal Khan; Umar Farooq; Farhan A Khan; Syed Majid Bukhari; Sher Bahadar Khan

doi:10.1016/S1875-5364(18)30021-9

Bioassay-guided isolation of novel and selective urease inhibitors from Diospyros lotus

Chin J Nat Med. 2017 Nov;15(11):865-870. doi: 10.1016/S1875-5364(18)30021-9.

Authors

Abdur Rauf¹, Ghias Uddin², Bina S Siddiqui³, Ajmal Khan⁴, Umar Farooq⁵, Farhan A Khan⁶, Syed Majid Bukhari⁶, Sher Bahadar Khan⁷

Affiliations

¹ Department of Chemistry, University of Swabi, Anbar-23561, Khyber Pakhtunkhwa, Pakistan.
² Institute of Chemical Sciences, University of Peshawar, Peshawar-25120, Pakistan.
³ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
⁴ Department of Chemistry, COMSAT Institute of Information Technology, Abbottabad-22060, Pakistan; UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Birkat Al-Mouz, Nizwa-616, Oman. Electronic address: ajmalkhan@ciit.net.pk.
⁵ Department of Chemistry, COMSAT Institute of Information Technology, Abbottabad-22060, Pakistan. Electronic address: umarf@ciit.net.pk.
⁶ Department of Chemistry, COMSAT Institute of Information Technology, Abbottabad-22060, Pakistan.
⁷ Center of Excellence for Advanced Materials Research (CEAMR), Department of Chemistry, Faculty of Science King Abdulaziz University, Jeddah 21589, Saudi Arabia Kingdom.

PMID: 29329614
DOI: 10.1016/S1875-5364(18)30021-9

Abstract

Two new dimeric naphthoquinones, 5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (1; Di-naphthodiospyrol D) and 5',8'-dihydroxy-5,8-dimethoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2; Di-naphthodiospyrol E), along with known naphthoquinones diospyrin (3) and 8-hydroxy diospyrin (4) were isolated from the chloroform fraction of extract of Diospyros lotus roots. Their structures were elucidated by advanced spectroscopic analyses, including HSQC, HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1-4 were evaluated for urease activity and phosphodiesterase-I, carbonic anhydrase-II and α-chymotrypsin enzyme inhibitory activities. Compounds 1 and 2 and their corresponding fractions showed significant and selective inhibitory effects on urease activities. The IC₅₀ values of 1 and 2 were 260.4 ± 6.37 and 381.4 ± 4.80 µmol·L^-1, respectively, using thiourea (IC₅₀ = 21 ± 0.11 µmol·L^-1) as the standard inhibitor. This was the first report demonstrating that the naphthoquinones class showed urease inhibition.

Keywords: Carbonic anhydrase-II; Diospyros lotus; Naphthoquinones; Phosphodiesterase-I; Urease inhibitory activities; α-Chymotrypsin.

MeSH terms

Biological Assay
Diospyros / chemistry*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Molecular Structure
Naphthoquinones / chemistry
Naphthoquinones / isolation & purification
Naphthoquinones / pharmacology*
Plant Extracts / chemistry
Plant Extracts / pharmacology*
Plant Roots
Urease / antagonists & inhibitors*

Substances

5',8'-dihydroxy-5,8-dimethoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone
5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone
Enzyme Inhibitors
Naphthoquinones
Plant Extracts
di-naphthodiospyrol
Urease
diospyrin