Nighat Sultana

Oleanolic acid and related derivatives as medicinally important compounds

Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives.

Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product

Medicinal plants are becoming an important research area for novel and bioactive molecules for drug discovery. Novel therapeutic strategies and agents are urgently needed to treat different incurable diseases. Many plant derived active compounds are in human clinical trials. Currently ursolic acid is in human clinical trial for treating cancer, tumor, and skin wrinkles. This review includes the clinical use of ursolic acid in various diseases including anticancer, antitumor, and antiwrinkle chemotherapies, and the isolation and purification of this tritepernoid from various plants to update current knowledge on the rapid analysis of ursolic acid by using analytical methods. In addition, the chemical modifications of ursolic acid to make more effective and water soluble derivatives, previous and current information regarding, its natural and semisynthetic analogs, focusing on its anticancer, cytotoxic, antitumor, antioxidant, anti-inflammatory, anti-HIV, acetyl cholinesterase, α-glucosidase, antimicrobial, and hepatoprotective activities, briefly discussion is attempted here for its research perspectives. This review article contains fourteen medicinally important ursolic acid derivatives and 351 references.

Protein glycation inhibitory activities of Lawsonia inermis and its active principles

The protein glycation inhibitory activity of ethanolic extract of Lawsonia inermis (henna) plant tissues was evaluated in vitro using the model system of bovine serum albumin and glucose. Protein oxidation and glycation are posttranslational modifications that are implicated in the pathological development of many age-related disease processes. This study investigated the effects of Lawsonia inermis ethanolic extract and its components, on protein damage induced by a free radical generator in in vitro assay system. We found that alcoholic extract of Lawsonia inermis can effectively protect against protein damage and showed that its action is mainly due to Lawsone. In addition, the presence of gallic acid also plays an important role in the protective activity against protein oxidation and glycation. Two known compounds, namely, Lawsone and gallic acid previously isolated from this plant were subjected to glycation bioassay for the first time. It was found that the alcoholic extract, lawsone (1) and gallic acid (2) showed significant inhibition of Advanced Glycated End Products (AGEs) formation and exhibit 77.95%, 79.10% and 66.98% inhibition at a concentration of 1500 μg/mL, 1000 μg/mL and 1000 μM respectively. Lawsonia inermis, compounds 1 and 2 were found to be glycation inhibitors with IC50 82.06 ± 0.13 μg/mL, 67.42 ± 1.46 μM and 401.7 ± 6. 23 μM respectively. This is the first report on the glycation activity of these compounds and alcoholic extract of Lawsonia inermis.

Malaria and artemisinin derivatives: an updated review.

Malaria is the worlds most prevalent disease that affects 515-600 million people each year and about 40% of the worlds population live at risk for this infection. The prevalence of morbidity and mortality from drug resistant malaria (Plasmodium falciparum) is increasing in most of the developing countries, which is also a global threat because international travel is common now and imported malaria is increasingly a serious problem. Since rapid schizonticidal action of naturally occurring endoperoxides pharmacophore present in artemisinin against drug-resistant malaria has been documented, researchers have focused more on artemisinin analogs than any other antimalarials. In this review, drugs of choice about malaria i.e. artemisinin and its analogus/derivatives (arteether, artemether, artemiside, artemisinin, artemisone, artesunate, dihydroartemisinin) have been discussed in detail e.g. bioavailability, formulation development, stability, combination therapy, additional benefits, drug resistance and toxicity have been reviewed.

New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids

During this study, one new coumarin; 7-O-β-D-glucopyranoside-2H-1-benzopyran-2-one (1) and three quinoline alkaloids; 3-hydroxy, 2, 2, 6-trimethyl–3, 4, 5, 6-tetrahydro-2H-pyrano[3,2-c] quinoline 5-one (2), ribalinine (3) and methyl isoplatydesmine (4) were isolated from the aerial parts of Skimmia laureola and their structures established by spectroscopic studies. Compounds 2-4 were found to be linear mixed type inhibitors of acetylcholinesterase (Ki = 110.0, 30.0 and 30.0 μM, respectively). Compounds 2 and 3 were also found to be linear mixed type inhibitors of butyrylcholinesterase, while compound 4 was a noncompetitive inhibitor of the enzyme (Ki = 90.0, 70.0 and 19.0 μM, respectively). The inhibition of acetyl- and butyryl-cholinesterase enzymes persists as the most promising therapeutic strategy for activating the impaired cholinergic functions in Alzheimers disease and related dementias. Compound 4 also showed dose-dependent spasmolytic activity in the isolated rabbit jejunum intestinal preparation by relaxing the spontaneous (EC50 = 0.1 mg/mL) and K+-induced contractions (EC50 = 0.4 mg/mL), suggesting that the spasmolytic effect of compound 4 is mediated through the blockade of voltage-dependent Ca2 + channels.

Microbial transformation of oleanolic acid by Fusarium lini and α-glucosidase inhibitory activity of its transformed products

The biotransformation of a pentacyclic triterpene, oleanolic acid (1), with Fusarium lini afforded two oxidative metabolites, 2α,3β-dihydroxyolean-12-en-28-oic acid (2), and 2α,3β,11β-trihydroxyolean-12-en-28-oic acid (3). Metabolite 3 was found to be a new compound. The structures were characterized on the basis of spectroscopic studies. These metabolites exhibited a potent inhibition of α-glucosidase enzyme.

Phytochemical Studies on Alstonia scholaris

Reinvestigation of the flowers of Alstonia scholaris of Pakistan origin have resulted in the isolation of three new triterpenoids, two of the ursane type, 3β -acetate-24-nor-urs-4,12-diene ester triterpene (1) and 3β -hydroxy-24-nor-urs-4,12,28-triene triterpene (2), and one of the oleanane type, 3,28-β - diacetoxy-5-olea-triterpene (3), together with two known triterpenes,α-amyrin acetate (4) and ursolic acid (5). This is the first report of the isolation of 4 and 5 from the flower part of this species. The structures of 1 - 5 were elucidated with the aid of extensive NMR-spectroscopic studies. Graphical Abstract Phytochemical Studies on Alstonia scholaris

Phytochemical Studies on Adhatoda Vasica Nees

Abstract A new triterpenoid, 3α-hydroxy-D-friedoolean-5-ene (1), along with the known compounds, epitaraxerol (2) and peganidine (3), which have been isolated for the first time from the aerial parts of Adhatoda vasica Nees. The structures of these compounds were elucidated by spectral studies. X- Ray diffraction studies on a bronchodilating and hypotensive principle of A. vasica, vasicinone (4), were also carried out.

Nematicidal natural products from the aerial parts of Rubus niveus

Studies on the aerial parts of Rubus niveus yielded six known compounds, 3,5-dihydroxy benzoic acid C7H6O4, (1), gallic acid C7H6O5 (2), ethyl galactoside (3), oleanolic acid (4), β-sitosterol (5) and 3-O-[β-D-galactopyranosyl-(12)-D-glucopyranoside (6). Besides this, a gallic acid derivative with methyl substitution was synthesised as tetramethyl gallate (3). Together with this derivative, compounds 1, 2, the alcohol soluble, chloroform soluble and petroleum ether soluble extracts of the aerial parts of R. niveus were screened for its nematicidal activity against freshly hatched second stage juveniles of Meloidogyne incognita (root-knot nematode), exhibiting 100, 94, 100, 52, 45 and 14% mortality, respectively of M. incognita after 48 h at 0.5% concentration. Compounds 1, 2 and 3 were found to be more potent than the nematicide Azadirachta indica at the same concentration. Negative results were obtained for nematicidal activity of the petroleum ether extract of R. niveus leaf extract. This is the first report on the isolation of chemical constituents as well as the nematicidal activity of compounds and any part of R. niveus.

Nematicidal natural products from the aerial parts of Buddleja crispa

Studies on the aerial parts of Buddleja crispa yielded 13 known compounds, nonyl benzoate, hexyl p-hydroxy-cinnamate, ginipin, gardiol, 1-heptacosanol, steroidal galactoside (22 R)-stigmasta-7,9 (11)-dien-22 β-ol-3β-O-β-D-galactopyranoside, 3-methoxy benzoic acid, β-sitosterol and ursolic acid. Besides this two iridoid galactosides buddlejosides A, buddlejosides B and a benzofuran-type sesquiterpene buddlejone have been isolated from the ETOAC fraction of B. crispa. Together with the above compounds, methyl benzoate (1) and 3-methoxy-4-hydroxy benzoic acid (2) were also isolated. Compound 2 (C8H8O4) was identified by comparison of its data with those reported earlier, which was originally isolated from Onosma hispidum, and this is the first report of its isolation from this species. For compounds 1 and 2, the total alcoholic soluble extract, methanol soluble, chloroform soluble, ethyl acetate soluble and petroleum ether soluble extract of the aerial parts of B. crispa were screened for nematicidal activity against nematodes of freshly hatched second-stage juveniles of Meloidogyne incognita (root-knot nematode), exhibiting 92%, 40%, 88%, 83%, 82% and 50% mortality, respectively, of eloids M. incognita at 0.5% concentration. Compound 1 was more potent than the nematicide Azadirachta indica at the same concentration. Negative results were obtained for the nematicidal activity of petroleum ether extract of B. crispa leaves.