Short Communication: Discovery and molecular docking simulation of 7-hydroxy-6-methoxy-2H-chromen-2-one as a LOX Inhibitor.

Millettia ovalifolia is traditionally used in variety of diseases including inflammation. In our investigation in to the phytochemical constituents of Millettia ovalifolia an effort was made to find out bioactive constituent from medicinal Plant M. ovalifolia to scientifically validate its use in inflammatory disorders. The compound 7-hydroxy-6-methoxy-2H-chromen-2-one was isolated from the bark of M. ovalifolia and was found to exhibited significant lipoxygenase (LOX) inhibitory activity with (IC50 value: 116.83±0.02µM). The Standard compounds Baicalein and Tenidap sodium revealed IC50 value being 22.1±0.03µM and 41.6±0.02µM. Molecular docking study further displayed significant molecular interactions between 7-hydroxy-6-methoxy-2H-chromen-2-one and LOX showed potential for further optimization as a possible anti-inflammatory lead compound.

Imaging prostate cancer (PCa) with [99m Tc(CO)3 ]finasteride dithiocarbamate.

This investigation aimed to modify finasteride (1) to finasteride dithiocarbamate (2) for subsequent synthesis of the rhenium analogue (3) and [99m Tc]tricarbonyl complexes (4), to assess its prostate cancer (PCa) targeting potential in a rat model. To validate the identity of (4), reference (3) has been synthesized by using fac-[Net4 ]2 [ReBr3 (CO)3 ] precursor and characterized by 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis. The analogue (4) was synthesized by using fac-[99m Tc(H2 O)3 (CO)3 ]+ precursor, and its structure was confirmed by comparative HPLC by using (3) as a reference. Further, the suitability of (4) as a PCa imaging agent was investigated in vitro and in vivo. At room temperature, (4) had ≥99% radiochemical purity and remained ≥84% stable in serum. In preclinical studies, biodistribution of (4) in histopathologically established rat model showed adequately high in vivo uptake in the prostate attracting the possibility of using it for noninvasive imaging of PCa.

Muscle relaxant activities of pistagremic acid isolated from Pistacia integerrima.

The aim of the current work was to explore the muscle relaxant effect of pistagremic acid (PA) isolated from Pistacia integerrima in various animal paradigms. In a rotarod test, PA caused a significant (p<0.05) muscle relaxant potential in a dose-dependent manner. When studied in the inclined plane test, pretreatment with PA (5 and 10 mg/kg) caused promising activity (p<0.05) after treatment for 30, 60 and 90 min. The muscle relaxant potential of PA was strongly complimented by the traction and chimney tests, showing a dominant effect after 60 min of treatment. In conclusion, PA possesses strong muscle relaxant activity in various animal-based models.

Multidrug resistance reversal activity of extract and a rare dimeric naphthoquinone from Diospyros lotus.

A dimeric naphthoquinone namely dihydrodyspyrole R (1) was purified once more from Diospyros lotus. Dihydrodyspyrole R and chloroform fractions were evaluated for their effects on the reversion of multidrug resistance (MDR). The compounds (1) and extract exhibited promising MDR reversing effect in a dose-dependent manner against mouse T-lymphoma cell line. Molecular docking of compound 1 revealed the correlation between in-silico with in-vitro results. The molecular docking results showed that compound 1 is bind closely where co-crystal ligand of P-gp is present. But usually, computational investigation predicts that, if a compound gives lesser score then compound will exhibit good activity. Hence, the docking scores of compound 1 are the near to the Rhodamine. It is conclude that there are certain important structural features of compound 1which are responsible for the inhibiting potency of P-gp from mice. The computational Petra/Osiris/Molinspiration (POM) analysis confirms the possibility of use of compound 1 without side effect or less toxicity risks.

Antinociceptive, antioxidant and phytochemical studies of Pakistani medicinal plants.

The aim of the current study was to evaluate the antinociceptive activity of the selected Pakistani medicinal plants (Chenopodium botrys, Micromeria biflora and Teucrium stocksianum) in-vivo followed by their antioxidant potential against 1,1-diphenyl-2-picrylhidrazyl (DPPH) in-vitro. The results demonstrated profound antinociceptive effect of both the crude methanolic extract of Chenopodium botrys (CBM) and subsequent aqueous fraction (CBW) of C. botrys with 80.76% and 84% pain relief in acetic acid induced writhing test at 100 mg/kg i.p respectively. Similarly the crude methanolic extract of Micromeria biflora (MBM) and its subsequent aqueous fraction (MBW) with 66.46% 78.08% pain reversal in acetic acid induced writhing test respectively at 100mg/kg i.p. However, the crude methanolic extract and isolated water fraction of Teucrium stocksianum (TS) did not show any significant effect at test doses. Both the crude extracts and aqueous fractions of selected medicinal plants exhibited marked scavenging effects on DPPH and therefore strongly support the antinociceptive activity. Phytochemical analysis indicated the presence of various classes of natural products (alkaloids, terpenoids, flavonoids etc.) and thus the current finding can be attributed to the presence of these compounds. In short, our findings provide a strong scientific background to the folk uses C. botrys and M. biflora in the management of various painful conditions.

Preliminary antioxidant profile of Pistacia integerrima Stewart.

To explore the free radical scavenging properties of crude ethanolic extract of galls, bark, leaves, roots of Pistacia integerrima and its subsequent solvent fractions viz., n-hexane, chloroform, ethyl acetate and methanol against 1, 1-diphenyl-2-picrylhydrazyl (DPPH) stable. In vitro DPPH based free radical was employed using querceitin as standard antioxidant while methanol as negative control. Different parts of P. integerrima showed marked scavenging on DPPH in a concentration dependent manner. The ethanolic extract exhibited 60.51 88.51% scavenging effect on DPPH which differentiated upon fractionation. of the part used, leaves of the plant were the least effective while n-hexane was the least dominant fraction. However, the rest of the parts and fractions demonstrated profound scavenging potential. This in-vitro study revealed an outstanding free radical scavenging potential of various solvent fractions of different parts of whole plant P. integerrima.

Preliminary phytochemical screening, antimicrobial and antioxidant activities of Euphorbia milli.

Euphorbia milii is a Pakistani herb used for various infectious diseases. In this study we have carried out phytochemical, antibacterial and antioxidant investigation of different extracts/fractions. Phytochemical studies showed the presence of cardiac glycosides, steroids/phytosterols, anthocyanin, proteins, terpenoids, flavonoids and tannins. Susceptibility testing by well diffusion assay of its chloroform and methanol fractions revealed good antimicrobial activity against Klebsiella pneumonia and Staph epidermis. Ethyl acetate fraction of roots also exhibited considerable antimicrobial activity against most of tested pathogens. Various fractions (Hexane, chloroform, methanol and water) of E. milii were screen for their antioxidant potential using DPPH radical scavenging assay at different concentrations among these, chloroform fraction exhibited good scavenging activity. The IR spectroscopy of the various extracts/fractions indicated the presence of OH, saturated CH stretching, C=C, C=O, NO2, C-N, Ar-O, C-O- and R-O-Stretching respectively. The findings provide helpful evidence for the use of E. milii in traditional medicines.

A comprehensive review on the ethnobotanical, phytochemical, and pharmacological aspects of the genus Malvastrum.

The genus Malvastrum, from the family Malvaceae, is a small genus of twenty four species, distributed worldwide. Some of the species have a long and rich history of ethnobotanical and traditional medicinal uses. Few reports of systematic scientific studies can be found in the literature which highlight the rich chemical profile and pharmacological properties of the genus. This is the first ever attempt to compile the available literature and provide a critical overview for future studies on the genus. For this purpose, several databases, such as PubMed, Scifinder, Elsevier, Google Scholar, and others were utilized. Literature records the presence of bioactive metabolites in the genus, effective against dysentery, gastrointestinal distress, fever, enteritis, hepatitis, cough, sore throat, arthritis, and diabetes. Seventy four biologically active secondary metabolites have been identified from different species of Malvastrum, including four pure isolates. Furthermore, this report also documents their potential properties. This article may prove as a milestone for new researchers, eager to work on Malvastrum species and perform further in-depth studies on this genus.

Pistagremic acid a new leishmanicidal triterpene isolated from Pistacia integerrima Stewart.

The present study was designed to investigate the whole plant of Pistacia integerrima Stewart in order to examine the pharmacological basis of the use of the plant in folk medicine for the treatment of infectious diseases and disorder. Phytochemical and pharmacological studies led to the isolation of a new triterpene pistagremic acid (3-methyl-7-(4,4,10,13,14-pentamethyl-3-2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-oct-3-enoic). Pistagremic acid showed significant leishmanicidal activity (IC(50): 6.71 ± 0.09 µM) against Leishmania major (DESTO) promastigotes in comparison to standard compound amphotericin B (IC(50): 0.21 ± 0.06 µM).

Ethnic uses, pharmacological and phytochemical profile of genus Grewia.

A number of species of genus Grewia have been used as medicinal agents to treat several diseases. This review based on 45 literary sources discusses the current knowledge of traditional uses, chemistry, biological effects, and toxicity of different species of this genus. Triterpenoids, steroids, glycosides, flavones, lignans, phenolics, alkaloids, lactones, anthocyanins, flavones, and organic acids have been isolated from various species of this genus. The extracts and preparations from the various plants, which are expectantly safe, exhibited various biological effects, e.g. anti-oxidant, anti-bacterial, hepatoprotective, anti-inflammatory, anti-emetic, anti-malarial, analgesic, and anti-pyretic activities.

Synthesis, Bioactivity Assessment, and Molecular Docking of Non-sulfonamide Benzimidazole-Derived N-Acylhydrazone Scaffolds as Carbonic Anhydrase-II Inhibitors.

This research reports the synthesis of new benzimidazole-derived N-acylhydrazones (NAH), their characterization using various spectroscopic methods, and in vitro evaluation as potent carbonic anhydrase-II inhibitors. Among the target compounds (9-29), few showed higher inhibition than the standard acetazolamide (IC50: 18.6 ± 0.43 µM), for example, compound 9 (IC50: 13.3 ± 1.25 µM), 10 (IC50: 17.2 ± 1.24 µM), 12 (IC50: 14.6 ± 0.62 µM), and 15 (IC50: 14.5 ± 1.05 µM). Molecular docking was performed on the most active compounds, which revealed their binding interactions with the active site of the enzyme, thus supporting the experimental findings.

2-Methyl-6-(4,4,10,13,14-penta-methyl-3-oxo-2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetra-deca-hydro-1H-cyclo-penta-[a]phenanthren-17-yl)hept-2-enoic acid.

In the title compound, C(30)H(46)O(3), an isolation product of Pistacia integerima Stewart, the five-membered ring is nearly in the envelope form. A 6-carb-oxy-hept-5-en-2-yl group is attached to the five-membered ring. An S(6) ring motif is formed due to intra-molecular C-H⋯O hydrogen bonding. In the crystal, inter-molecular O-H⋯O hydrogen bonds form carboxyl-ate dimers with R(2) (2)(8) ring motifs.

Green synthesis and biomedicinal applications of silver and gold nanoparticles functionalized with methanolic extract of Mentha longifolia.

This study deals with facile and rapid synthesis of silver nanoparticles (AgNPs) and Gold nanoparticles (AuNPs) using Mentha longifolia leaves extracts (MLE). The synthesized AgNPs and AuNPs were characterized by UV-visible spectroscopy (UV-Vis), Fourier transformed infra-red spectroscopy (FT-IR), atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. The phytochemical analysis showed the presence of bioactive secondary metabolites, which are involved in the synthesis of nanoparticles (NPs). The surface plasmon resonance (SPR) observed at 435 and 550 nm, confirmed the green synthesis of AgNPs and AuNPs, respectively. The TEM images showed poly dispersed and round oval shapes of Ag and Au NPs with an average particles size of 10.23 ± 2 nm and 13.45 ± 2 nm, respectively. TEM results are in close agreements with that of AFM analysis. The FT-IR spectroscopy revealed the presence of OH, -NH2 and C = O groups, which involved in the synthesis of NPs. The MLE and their AgNPs and AuNP exhibited good in vitro antibacterial and anti-oxidant activities. Moreover, MLE and NPs also showed in vivo analgesic activities in mice, and excellent sedative properties in open field test paradigm.

Diospyros, an under-utilized, multi-purpose plant genus: A review.

The genus Diospyros from family Ebenaceae has versatile uses including edible fruits, valuable timber, and ornamental uses. The plant parts of numerous species have been in use as remedies in various folk healing practices, which include therapy for hemorrhage, incontinence, insomnia, hiccough, diarrhea etc. Phytochemical constituents such as terpenoids, ursanes, lupanes, polyphenols, tannins, hydrocarbons, and lipids, benzopyrones, naphthoquinones, oleananes, and taraxeranes have been isolated from different species of this genus. The biological activities of these plants such as antioxidant, anti-inflammatory, analgesic, antipyretic, anti-diabetic, antibacterial, anthelmintic, antihypertensive, cosmeceutical, enzyme-inhibitory etc. have been validated by means of an in vitro, in vivo, and clinical tests. As a rich reserve of pharmacologically important components, this genus can accelerate the pace of drug discovery. Accordingly, the aim of the present review is to survey and summarize the recent literature pertaining to the medicinal and pharmacological uses of Diospyros, and to select experimental evidence on the pharmacological properties of this genus. In addition, the review also aims at identifying areas that need development to make use of this genus, especially its fruit and phytochemicals as means for economic development and for drug discovery.

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

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.

In vivo and in silico sedative-hypnotic like activity of 7-methyljuglone isolated from Diospyros lotus L.

Diospyros lotus L. possesses different therapeutic activities such as antioxidant, anti-proliferative, anti-microbial and sedative. However, no studies on the sedative-hypnotic activity of 7-methyljuglone are reported. In the present study, we have evaluated in vivo the anxiolytic-hypnotic like effects of 7-methyljuglone in mice with open field and phenobarbitone-induced sleeping time tests. We have also assessed in silico the involvement of GABAA, GABAB and 5HT1 neurotransmission in its mechanism of action. The intraperitoneal administration of 7-methyljuglone (2.5-10mg/kg) reduce significantly the number of crossed lines in mice open field test and concomitantly it shown a significant activity in term of onset of sleeping time and also in its duration. Moreover, 7-methyljuglone demonstrated in silico an interesting interaction with GABAA but not GABAB and 5HT1binding sites. All of these results, taken together, 7-methyljuglone may be an innovative candidate for designing new pharmaceutical and therapeutic applications.

Phytochemical, ethnomedicinal uses and pharmacological profile of genus Pistacia.

Pistacia genus belong to family Anacardiaceae and it is versatile in that its member species have food (P. vera), medicinal (P. lentiscus) and ornamental (P. chinensis) values. Various species of this genus have folkloric uses with credible mention in diverse pharmacopeia. As a trove of phenolic compounds, terpenoids, monoterpenes, flavonoids, alkaloids, saponins, fatty acids, and sterols, this genus has garnered pharmaceutical attention in recent times. With adequate clinical studies, this genus might be exploited for therapy of a multitude of inflammatory diseases, as promised by preliminary studies. In this regard, the ethnomedicinal, phytochemistry, biological potencies, risks, and scopes of Pistacia genus have been reviewed here.

Urease inhibition potential of Di-naphthodiospyrol from Diospyros lotus roots.

The dimeric napthoquione 5,8,4'-trihydroxy-1'-methoxy-6, 6'-dimethyl-7,3'-binaphtyl-1,4,5',8'-tetraone (1) was isolated from the chloroform fraction of Diospyros lotus extract. Compound 1 was screened for its inhibitory effects against four enzymes: urease, phosphodiesterase-I, carbonic anhydrase-II and α-chymotrypsin, and showed selective activity against urease enzyme with an IC50 value of 254.1 ± 3.82 µM as compared to the standard thiourea (IC50 = 21 ± 0.11 µM). Furthermore, in silico docking study was carried out to explain the molecular mechanism of compound 1 against the target receptor.

Sedative-hypnotic-like effect and molecular docking of di-naphthodiospyrol from Diospyros lotus in an animal model.

BACKGROUND: Diospyros lotus Linn commonly known as date-plum, or Caucasian persimmon has multiple uses in folk medicine. Various parts of this plant is used for alleviating lumbago, dysponea, hemorrhage, insomnia, and hiccup. The plant extracts possess a variety of biological activities, such as anti-inflammatory, sedative, febrifuge, anti-microbial, vermifuge, and anti-hypertensive. AIM/HYPOTHESIS: The aim of the present work is to investigate the sedative-hypnotic effect of a rare dimeric napthoquione 1 obtained from the chloroform soluble fraction of D. lotus extracts. METHODS: Compound 1, di-naphthodiospyrol at 5, 10, and 15mg/kg intraperitoneal doses was assessed for its in vivo sedative effect in an open-field using a phenobarbitone-induced sleeping time model. The geometry of di-naphthodiospyrol was also optimized with the aid of density functional theory. In addition, molecular docking of compound 1 was performed with the receptor GABAA. RESULTS: The animal protocol-based assay showed significant sedative-hypnotic-like effects of compound 1 at various test doses (5, 10, and 15mg/kg i.p.). Docking studies indicated that this compound interacts strongly with important residues in receptor GABAA. CONCLUSIONS: Results from this investigation reveal that compound 1 possesses sedative-hypnotic- like properties which can be of interest in therapeutic research.

Gastrointestinal Motility and Acute Toxicity of Pistagremic Acid Isolated from the Galls of Pistacia integerrima.

BACKGROUND: Pistacia integerrima has many medicinal uses in therapeutic as well as folk medicine. P. integerrima has been used for the treatment of different ailments such as blood purifier, anti-inflammatory, and as remedy for gastrointestinal disorders such as vomiting and diarrhea, expectorant, cough, asthma and fever. OBJECTIVE: The main objective of this research work was to evaluate the effect of pistagremic acid (PA) isolated from the galls of Pistacia integerima in acute toxicity and gastrointestinal (GIT) motility tests. METHODS: Compound 1 namely pistagremic acid (PA) (at 10, 50, 100 mg/kg i.p) were assessed for their in-vivo gastrointestinal motility test using charcoal screening model. RESULTS: Results revealed that pretreatment of PA exhibited substantial safety in acute toxicity test up to the dose of 500 mg/kg p.o. However, when studied in charcoal meal GI transit test, PA caused significant (p < 0.05) attenuation of GIT motility and an increase in intestinal transit time, comparable to atropine (a muscarinic receptor blocking agent). CONCLUSION: In conclusion, PA displayed a strong dose-dependent reduction in GIT motility with considerable safety.