Sajal Srivastava

POM analyses of antimicrobial activity of some 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes: favourable and unfavourable physico-chemical parameters in design of antibacterial and mycolytic agents

In the present contribution, we have used petra, osiris and molinspiration (POM) analyses to identify pharmacophores and anti-pharmacophores for antibacterial/antifungal activity of some benzothiophene derivatives (THBT). Lipophilicity and presence of tautomerism processes were the major factors that governed the orientation to antibacterial and/or antiviral activity. It was also observed that these compounds POM analyzed have a closed pharmacophore site which might be bioactivity low. Further, we have carried out receptor-based electrostatic analysis to confirm the electronic, steric and hydrophobic requirements for future modifications. The POM analyses provide substantial idea about the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the drug-resistant microorganisms.Graphical AbstractThe impact of intramolecular OH/N and NH/N interactions on bioactivity of pharmacophores sites of THBT series 5–15 is established. The POM analyses of 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes (THBT) 5–15 provide substantial idea about the structural features responsible for their failure as dual antibacterial/antifungal agents and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the bacterial and fungal enzymes responsible of diseases.

POM analyses for antimicrobial evaluation of thienopyrimidinones derivatives: a rapid method for drug design

AbstractIn this work, a new and efficient strategy to identify pharmacophores and anti-pharmacophores sites in thienopyrimidinone derivatives for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses is described. We carried out receptor based electrostatic analysis to confirm the electronic, steric and hydrophobic requirements for further modifications. Results showed that the major factors that govern the orientation to antibacterial/antiviral activity were of lipophilicity and presence of tautomerism. In addition, POM analyzed compounds constitute different supplementary attractive active sites that possess significant bioactivity and qualify them as promising candidates that might be responsible to inhibit kinase enzymes. Furthermore, the POM analyses provide substantial idea about the structural features of thienopyrimidinone derivatives in relation to biological activities against disease causing agents. Our results suggest future work on these POM assessed derivatives to evaluate their toxicity in human cells and selectivity which improve activity against cancer causing kinase enzymes by developing target oriented new drugs to save humanity.Graphical AbstractThe identification of potential combined antibacterial/ antifungal and antitumor pharmacophores sites of 4-12, using POM analyses, is the crucial step in optimization of hits. The POM analyses of thienopyrimidinones 4-12 provide substantial idea about the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the kinase enzyme responsible of cancer.

Hepatoprotective effect of Ethanolic Extract of Holarrhena antidysenterica against Paracetamol Induced Toxicity in Wistar Rats

Background: Holarrhena antidysenterica L. traditionally treats amoebic dysentery, diarrhoea, asthma, bronchopneumonia, malaria and some other disorders. Aim: The current study was designed to explore the effects and possible mechanisms of Holarrhena antidysenterica on paracetamol induced hepatic damage in a rat model. Materials and methods: The Hepatic damage was induced in male wistar rats with PCM (2g kg-1) administration for 4 weeks. Liver histopathological study was performed, and the liver function was performed by determining the (SGPT) Serum glutamate pyruvate transaminase, (SGOT) Serum glutamic oxaloacetic transaminase, Alkaline phosphatase (ALP) and Total bilirubin (TB) for evaluating the effect of HAE on hepatic damage. The possible mechanisms were investigated by measuring hepatic collagen metabolism and oxidative stress level. Findings: HA extract care significantly inhibited the loss of liver weight induced by PCM. Then the HAE improved the liver function of rats as recorded by decreased serum enzymatic activities of SGPT, SGOT ALP and TB (p<0.05, p<0.01). Histopathological results indicated that HAE alleviated liver damage and reduced the formation of fibrous septa. Moreover, HAE significantly decreased liver Hydroxyproline (Hyp) content. It also decreased liver Malondialdehyde concentration, increased activities of liver superoxide dismutase, catalase, and glutathione peroxidase. The hematological Parameter induced by HAE is normal compared with the control. The standardized extract HPTLC investigation uncovered the presence of some critical phenolic compound. Conclusion: This examination demonstrated that Holarrhena antidysenterica could be taken as a decent common wellspring of the hepatoprotective agent.

The Indian Magical Herb ‘Sanjeevni’ (Selaginella bryopteris L.) - A Promising Anti-inflammatory Phytomedicine for the Treatment of Patients with Inflammatory Skin Diseases

Objectives Selaginella bryopteris L. (family: Selaginaceae), is often used in traditional Indian systems of medicine for the prevention and cure of several disorders and for the treatment of patient with spermatorrhoea, venereal disease, constipation, colitis, urinary tract infections, fever, epilepsy, leucorrhoea, beri-beri and cancer. It is also used as a strength tonic. This study aimed to evaluate the mechanisms underlying the anti-inflammatory effects of topically administered aqueous, polar and non-polar methanolic fractions (10 mg/20 μL) of Selaginella bryopteris. Methods An acute oral toxicity study of Selaginella bryopteris at doses from 250 to 2,000 mg/kg body weight (bw) was performed. Aqueous, polar and non-polar methanolic extracts (10 mg/20 μL) applied topically for 5 days were evaluated for their anti-inflammatory effects against 12-tetra-O-decanoyl phorbol acetate (TPA)-induced inflammation by using the redness in the ear, the ear’s weight (edema), oxidative stress parameters, such as lipid-peroxide (LPO) and nitric oxide (NO), and the pro-inflammatory cytokines involved in inflammation, such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. Indomethacine (0.5 mg/20 μL) was used for the positive control. Results Selaginella bryopteris produced no mortalities when administered orally at doses from 250 to 2,000 mg/kg bw. Topical treatment with the non-polar methanolic fraction (10 mg/20 αL) significantly suppressed redness (2.4 ± 0.5) and edema (30.4 ± 1) and effectively reduced the LPO level (32.3 ± 3.3). The NO level was (8.07 ± 0.55), and the TNF-α, IL-1β, and IL-6 levels were decreased to 69.6 ± 15.5, 7.7 ± 4.8 and 82.6 ± 5.9, respectively. Conclusion This study demonstrated for the first time the mechanisms underlying the anti-inflammatory effect of medicinal plants like Selaginella bryopteris and quantified the pharmacological interactions between them. The present study showed this herbal product to be a promising anti-inflammatory phytomedicine for the treatment of patients with inflammatory skin diseases.

Ulcer healing potential of ethanolic extract of Caralluma attenuata on experimental diabetic rats

Introduction: Available data indicated that diabetes mellitus (DM) increases the vulnerability of the gastric ulcers and the need of the hour is to develop effective agents to treat ulcer with diabetes for better patient compliance and cost effectiveness. The ulcer-healing properties of ethanolic extract of Caralluma attenuata (CAEt) against both chemically- and physically induced gastric ulcers in experimental rats are recently studied. Aim: To assess the ulcer healing potential of Ethanolic Extract of Caralluma attenuata on Experimental Diabetic Rats. Material and Methods: The current study aimed to evaluate ulcer healing properties of CAEt on the aspirin induced gastric ulcer in rats with streptozotocin induced DM. The hypothesis is based on the fact that DM results in compromising the mucosal defensive factors associated with delay in gastric ulcer healing, and if these changes can be corrected by using agents known for their antidiabetic and antiulcer properties. Experimental albino rats were divided into six groups. Except for Group I, other groups contained streptozotocin-induced diabetic rats. Group I (normal control) and Group II (diabetic control) were administered vehicle, Groups III and IV (diabetic experimental) were administered CAEt in dose of 100 mg/kg and 250 mg/kg, respectively, and Groups V and VI (positive controls) were respectively administered oral standard drugs omeprazole, 20 mg/kg, and tolbutamide 10 mg/kg. Result: The results confirmed that the CAEt significantly decreases the ulcer index (P < 0.05) in the aspirin-induced gastric ulcers and also significantly exhibit antioxidant and glucose lowering activity in the diabetic ulcer rats. The study showed that C. attenuata has the potential to be used as an antiulcer agent in experimental diabetic rats.