COMPUTATIONAL APPROACHES RELATED TO DRUG DISPOSITION

Drug disposition connects with the movement of drug molecules inside the body after administration irrespective with the route of administration. After entering the system, drug molecule and internal body systems comes under various pharmacokinetic interactions followed by observation of suitable biological activity. In this exhaustive process, physicochemical nature of the chemical substance and physiological nature of system makes this movement competitive. In this view, pharmacokinetic and toxic properties of the molecule regulates the destination of the molecule. Various computational processes are available for in silico pharmacokinetic assessment of drug molecule after absorption through biological membrane, distributed throughout the system based on the percent ionization or partition coefficient factors followed by biologically transformed into an another entity in presence of microsomal enzymes and finally excrete out from system using various cellular transport systems as well as related cellular toxicity behavior. In this chapter, we ensemble all the possible information related with the drug movement and related computational tools to understand the possible chemical and pathophysiological changes. Here detailed knowledge on database expedition, establishment of pharmacophore model, homology modelling based on sequence similarity, molecular docking study (rigid and flexible docking) and QSAR/QSPR study (with detailed process and available softwares) are provided. These diversely united informations actually helps a researcher to understand the factual movement of a drug molecule inside the system

RECENT DEVELOPMENTS AND MULTIPLE BIOLOGICAL ACTIVITIES AVAILABLE WITH 1, 8-NAPHTHYRIDINE DERIVATIVES: A REVIEW

Within the wide range of nitrogen-containing heterocyclic compounds, the derivatives of 1,8-naphthyridine (NPTR) have gained a rising interest due to their reported versatile biological activities. The derivatives of NPTR scaffold are found to invite special interest from researchers nowadays on the significance of their manifestations of multiple attractive pharmacological activities which establish them as an effective and versatile tool in pharmaceutical chemistry and drug discovery. The diverse biological activities mainly include anti-inflammatory, antimicrobial, antiviral, anticancer, antihypertensive and analgesic activities. Novel NPTR scaffold has emerged its potency to treat neurological diseases like depression and Alzheimer's disease. Further these agents possess different inhibitory activities, such as anti-HIV, anti-osteoporotic, αvβ3 antagonism, antimalarial, platelet aggregation, anti-oxidant, anti-allergic, gastric antisecretory, anticonvulsant, epidermal growth factor receptor (EGFR) inhibition, protein kinase inhibition, ionotropic properties, β3 antagonism, phosphodiesterase 4 (PDE 4) inhibitions, adenosine receptor agonistic activity, adrenoceptors antagonism and DNA stabilizing activity, etc. In this review, we highlight the updates of different 1,8-naphthyridine derivatives and explain the key data available in the context of various biological activities of NPTR derivatives available from the literature. This may direct opportunity in researches in the synthesis of novel medicinal agents and the development of new heterocycles for modification of existing biological actions as well as evaluation of other possible pharmacological activities

LYSOSOMAL MEMBRANE AND PROTEIN STABILIZATION BY DALBERGIA SISSOO (FAMILY: FABACEAE): IN VITRO ANTI-INFLAMMATORY ACTIVITY

Objective: Plants of the genus Dalbergia are reported to be useful in the treatment of arthritis, gonorrhoea and rheumatic pains. Present study was aimed to investigate the in vitro anti-inflammatory activity of ethanol extract from Dalbergia sissoo leaves (EDS) and to support its traditional use.Methods: EDS was investigated for it's in vitro anti-inflammatory activity in human red blood cell membrane stabilization (HRBC) method and protein denaturation method. Diclofenac sodium was used as the standard drug.Results: The EDS and diclofenac sodium showed a concentration dependent stabilization toward HRBC membrane with 314.3±0.01 and 34.91±0.01 µg/ml; 50% protection, respectively. EDS and diclofenac sodium also showed dose dependent protein denaturation with IC50 values 719.9±0.04 and 428.4±0.02 µg/ml, respectively.Conclusions: EDS possessed noticeable in vitro anti-inflammatory effect against the HRBC membrane stabilization method and denaturation of albumin. Further authoritative studies are necessary to make certain the mechanisms and constituents behind its anti-inflammatory actions.Â

ANTIHYPERGLYCEMIC ACTIVITY OF PHENYL AND ORTHO-HYDROXY PHENYL LINKED IMIDAZOLYL TRIAZOLO HYDROXAMIC ACID DERIVATIVES

Objective: The paradigm was to establish phenyl and ortho-hydroxy phenyl linked imidazolyl triazolo hydroxamic acid derivatives as an antihyperglycemic agent.Methods: 100 mg/Kg body weight dose of phenyl and ortho-hydroxy Phenyl linked Imidazolyl triazolo Hydroxamic Acid derivatives (FP1-FP12) and standard glibenclamide were administered per os (p.o.) in the streptozotocin-induced hyperglycemic rats by glucose oxidase-peroxidase method and statistically evaluated by one way analysis of variance.Results: FP3 was potent as compare to standard glibenclamide (P < 0.05-0.001) and FP6, FP9, and FP4 were also effective as an antihyperglycemic agent. The activity profile of the molecule was as follows FP9< FP10< FP4< FP6<FP12< FP3. This study reflects that presence of para methoxy phenyl group linked with phenyl group in surface recognition portion and imidazolyl triazole group in linker portion associated with a sulfamethyl hydroxamic acid group in metal identifying the part in case of FP3 was resemble for antihyperglycemic activity.Conclusion: It was concluded that compounds possessing electron releasing groups on the aromatic rings in the surface recognition part considerably enhanced the antihyperglycemic activity

Design, synthesis and antiproliferative activity of hydroxyacetamide derivatives against HeLa cervical carcinoma cell and breast cancer cell line

Purpose: To design and develop a new series of histone deacetylase inhibitors (FP1 - FP12) and evaluate their inhibitory activity against hydroxyacetamide (HDAC) enzyme mixture-derived HeLa cervical carcinoma cell and MCF-7.Methods: The designed molecules (FP1 - FP12) were docked using AUTODOCK 1.4.6. FP3 and FP8 showed higher interaction comparable to the prototypical HDACI. The designed series of 2-[[(3- Phenyl/substituted Phenyl-[4-{(4- (substituted phenyl)ethylidine-2-Phenyl-1,3-Imidazol-5-One}](-4H- 1,2,4-triazol-5-yl)sulfanyl]-N-hydroxyacetamide derivatives (FP1-FP12) was synthesized by merging 2- [(4-amino-3-phenyl-4H- 1, 2, 4-triazol-5-yl) sulfanyl]- N-hydroxyacetamide and 2-{[4-amino-3-(2- hydroxyphenyl)-4H-1,2, 4-triazol-5-yl]sulfanyl}-N hydroxyacetamide derivatives with aromatic substitutedoxazolone. The biological activity of the synthesized molecule (FP1-FP12) was evaluated against HDAC enzyme mixture-derived HeLa cervical carcinoma cell and breast cancer cell line (MCF-7).Results: HDAC inhibitory activity of FP10 showed higher IC50 (half-maximal  concentration inhibitory activity) of 0.09 μM, whereas standard SAHA molecule showed IC50 of 0.057 μM. On the other hand, FP9 exhibited higher GI50 (50 % of maximal concentration that inhibited cell proliferation) of 22.8 μM against MCF-7 cell line, compared with the standard, adriamycin, with GI50 of (-) 50.2 μM.Conclusion: Synthesis, spectral characterization, and evaluation of HDAC inhibition activity and in vitro anticancer evaluation of novel hydroxyacetamide derivatives against MCF-7 cell line have been achieved. The findings indicate the emergence of potentialanticancer compounds.Keywords: Molecular docking, Hydroxyacetamide derivative, Histone deacetylase inhibition activity, MCF-7 cell lin

A REVIEW ON BIOLOGICAL ACTIVITIES AND MEDICINAL PROPERTIES OF CLERODENDRUM INFORTUNATUM LINN

India has a great wealth of various naturally occurring herbal drugs which have great potential pharmacological and physiological activities. Since ancient times, several diseases have been treated by the administration of plant parts based on traditional and folk uses. Clerodendrum infortunatum Linn is one of them. Considerable utilisation and progress have been achieved regarding its biological activities. The whole parts of the plant contain different medicinally active substances which were variously used in Ayurveda, Unani and Homeopathy system of medicines. Its root, leaf and stem extract are used in microbial infection. Leaf extract is used as anthelmintic, analgesic, anticonvulsant, antidiabetic agent and also to increase haemoglobin level in the blood. Clerodolone, clerodone, clerodol are different isolated compounds obtained from this plant. A sterol, now designated as clerosterol obtained from the leaves and roots of C. infortunatum is used as an antitumor agent. This communication explains the evidence-based information regarding the different pharmacological activities with a correlation of chemical constituents available with this plant so that it may serve as a reference for further studies

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL EVALUATION OF SOME 1, 2, 4-TRIAZOLE DERIVATIVES

Objectives: To synthesize, characterize and evaluate antimicrobial properties of some 1, 2, 4-triazole derivatives. Methods: A novel series of 1, 2, 4-Triazole derivatives (D-1-D-8) had been synthesized. Ethyl esters of benzoic and 4-substituted benzoic acids were synthesized using ethanol and conc. sulphuric acid. In the second step, hydrazides of these esters were prepared. This hydrazide was converted into potassium salt of dithiocarbazinate using carbon disulfide and potassium hydroxide which on cyclization formed compounds (D-1-D-2). Compound D-3 was formed by reacting D-1 with 4-methylbenzenesulfonyl chloride in dry pyridine. Compounds (D-4-D-8) were synthesized by mixing aqueous solution of 10% NaOH in different primary amines and then heating it with potassium salt of dithiocarbazinate. The structures of newly synthesized compounds were established on the basis of 1H NMR and Mass spectroscopic techniques. The newly synthesized compounds were screened for their in vitro antibacterial and antifungal activity. In vitro antibacterial and antifungal activity was evaluated by Disc Diffusion method. Ofloxacin and Clotrimazole were used as standard drug respectively. Results: The results revealed that compounds D-3 and D-4 exhibited good antibacterial activity and D-1 and D-2 had moderate antibacterial activity as compared with standard drug Ofloxacin, while compounds (D-5-D-8) exhibited moderate antifungal activity as compared to standard drug Clotrimazole. Conclusion: A novel series of 1, 2, 4-Triazole derivatives were synthesized and were obtained in good yields. Newly synthesized compounds were isolated and purified by thin layer chromatography and column chromatography respectively

Celsia coromandeliane Vahl-A New Biomarker with Immense Pharmaceutical Applications

Plant derived products have been important source of therapeutic agents, and now days most of the drugs are plant derived products or their derivatives. In many cases, when a plant becomes commercialized as herbal medicine, or when one of its constituents starts getting used as a pharmaceutical drug. Although herbal medicines are less potent in comparison to synthetic drugs in some cases but still these are consider less toxic or having less side effect in contrast to synthetic drugs. Objective: The present review work aims to evaluate the medicinal importance of Celsia coromandeliane Vahl. Celsia coromandeliane Vahl, is common throughout India found widely in the plains throughout India including Chhattisgarh state. Conclusion: The review of literature study suggests that, plant is found to possess various medicinal activities like antibacterial, in vitro antioxidant, anthelmintic, and CNS depressant activity. It contains sigma steroidal derivatives which has effect on puberty. Secondary metabolites present in the plant are responsible for CNS Depressant effects, Antibacterial activities, and Anthelmintic activity. Keywords: CNS Depressant effects, Antibacterial activities, Anthelmintic activit