Saud Bawazeer

Antimicrobial Activity of Some Novel Armed Thiophene Derivatives and Petra/Osiris/Molinspiration (POM) Analyses

Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6–8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, 1H-13C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn’t guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.

Urease inhibition potential of Di-naphthodiospyrol from Diospyros lotus roots

Abstract 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.

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.

Mechanisms Underlying Anti-hyperalgesic Properties of Kaempferol-3,7- di-O-α-L-rhamnopyranoside Isolated from Dryopteris cycadina

BACKGROUND The present study was designed to evaluate the anti-hyperalgesic effect of kaempferol-3,7-di-O-α-L-rhamnopyranoside isolated from the ethyl acetate soluble part of Dryopteris cycadina. Pretreatment of the compound at the doses of 2.5, 5, and 10 mg/kg caused a significant reduction in abdominal constrictions in acetic acid-induced writhing test with maximum effect of 63.03% (P < 0.001) at 10 mg/kg i.p. When subjected in formalin test, it evoked a marked antinociceptive effect in both phases in a dose-dependent manner. The maximum (p < 0.01) pain-inhibiting effects were 61.36% and 65.89% in 1st and 2nd phases at 10 mg/kg i.p., respectively. Administration of atropine (non-selective cholinergic receptor antagonist) significantly (p < 0.05) antagonized the antihyperalgesic effect of the compound, while glibenclamide and naloxone did not alter the induced antinociceptive effect and thus, antinociceptive activity of the compound is mediated, at least in part, through cholinergic system antagonism; independent of calcium channel and opioidergic receptor participation. Furthermore, docking studies underlined strong COX-2 inhibitory activity of the compound. RESULT Our data concluded that overall analgesic activity of the compound seems to involve COX-2 inhibition and activation of cholinergic receptors. However, further detailed studies are required in this direction to confirm the analgesic effect of the compound for its possible clinical utility.

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.

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.

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.

How to improve antifungal bioactivity: POM and DFT study of some chiral amides derivatives of diacetyl-L-tartaric acid and amines

A computational Petra/Osiris/Molinspiration and Density Functional Theory based model has been developed for the identification of physic–chemical parameters governing the bioactivity of chiral amides derivatives of diacetyl-L-tartaric acid and aromatic amines 4–9 containing combined antifungal pharmacophore sites. The six compounds 4–9 analyzed here were previously experimentally and now virtually screened for their antibacterial/antifungal activity. The highest antifungal activity was obtained for compound 6, which exhibited excellent % inhibition, comparable to Terbinafine. Compound 5, represents increased activity as compared to its isomer 6. The increase of bioactivity from 5 to 6 could be attributed to the existence of pi-charge transfer from para-Bromo-phenyl to its amid group (COδ−--NHδ+), which plays a crucial template role in the organization of antifungal O,O-phramacophore sites. Moreover, it is cheap, has fewer side effects, and its possible inclusions in selective fungal/viral media such as Fusarium, HIV, and Hepatitis B/C have to be questioned.

Muscle relaxant activities of pistagremic acid isolated from Pistacia integerrima

Abstract 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.

Antidepressant Potential of Peptides: New Insights as Future Therapeutic

BACKGROUND & OBJECTIVE Clinical depression is an unsatisfactory mood disorder affecting millions of people worldwide. The disorder is associated with a phenomenal number of suicidal attempts each year, and it has been estimated that 10-20 million people around the world made an attempt of suicide in some stage of the disease. Thus, medicinal intervention is ultimately required to avoid such type of extreme outcomes. There are numerous therapeutic antidepressant options in clinical practice, however, most of them face the challenge of efficacy, side effects, and patient compliance. In this scenario, new effective and safe therapeutic agents are becoming the major focus of researchers in the area of neuropharmacology, who and are evaluating different sources such as synthetic and natural therapeutics. Similarly, thousands of peptides have already shown vital role in human physiology for regulation of different activities. CONCLUSION This mini-review will focus on peptides with reported antidepressant activity, along with their mechanism of action. Furthermore, the present article summarizes the literature pertaining to these peptides as antidepressant agents.