Virtual Screening, Molecular Docking and QSAR Studies in Drug Discovery and Development Programme

Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two basic approaches of computer-aided drug design (CADD) used in modern drug discovery and development programme. Virtual screening (or in silico screening) has been used in drug discovery program as a complementary tool to high throughput screening (HTS) to identify bioactive compounds. It is a preliminary tool of CADD that has gained considerable interest in the pharmaceutical research as a productive and cost-effective technology in search for novel molecules of medicinal interest. Docking is also used for virtual screening of new ligands on the basis of biological structures for identification of hits and generation of leads or optimization (potency/ property) of leads in drug discovery program. Hence, docking is approach of SBDD which plays an important role in rational designing of new drug molecules. Quantitative structure-activity relationship (QSAR) is an important chemometric tool in computational drug design. It is a common practice of LBDD. The study of QSAR gives information related to structural features and/or physicochemical properties of structurally similar molecules to their biological activity. In this paper, a comprehensive review on several computational tools of SBDD and LBDD such as virtual screening, molecular docking and QSAR methods of and their applications in the drug discovery and development programme have been summarized. Keywords: Virtual screening, Molecular docking, QSAR, Drug discovery, Lead molecul

Method Development and Validation of Gemifloxacin in Tablet Dosage Form by RP-HPLC

A simple, precise and accurate RP-HPLC method was developed and validated for the estimation of gemifloxacin in the tablet dosage form. The separation was achieved on a reversed-phase C-18 column (250 x 4.6 mm i.d., 5 µm) using a mobile phase consisting of acetonitrile/acetate buffer of pH 4.5 (70:30 v/v) at a flow rate of 1.0 ml/min and a detection wavelength of 244 nm. The separation was carried out on an isocratic mode at room temperature. The method was validated as per ICH guidelines for linearity, accuracy, precision, robustness, LOD, LOQ and specificity. The developed method showed good linearity over the concentration range of 50-150 µg/ml (r2=0.995). The average percentage recovery was 99.77%. The LOD and LOQ were 12.678 µg/ml and 14.261 µg/ml, respectively. Based upon validation studies, the developed method can be successfully applied for the routine analysis of gemifloxacin in bulk drugs as well as pharmaceutical dosage forms. Keywords: Gemifloxacin, Tablet dosage form, RP-HPLC, Validation, ICH guideline

Antidiabetic activity of Carallia brachiata Lour. leaves hydro-alcoholic extract (HAE) with antioxidant potential in diabetic rats

18-29Ethnomedicinal surveys have documented the traditional use of Carallia brachiata (Lour.) Merill (Rhizophoraceae) leaves in the management of diabetes mellitus in the Northeastern region of India. This study screens the hydro-alcoholic extract (HAE) of C. brachiata leaves for antioxidant and antidiabetic activities. The HAE was prepared using ethanol:water (7:3) by cold maceration method. The antidiabetic activity of HAE was evaluated in vivo in streptozotocin-induced diabetic rats at the doses of 250 or 500 mg/kg body weight for 21 days. The extract was also evaluated for in vitro and in vivo antioxidant activity. Results revealed that HAE of C. brachiata leaves possesses good hypoglycemic activity in diabetic rats. The hypoglycemic activity of HAE was found significant as compared to normal rats. Results of antioxidant activity were found statistically significant compared to standard drugs, quercetin and gallic acid. Results indicated a possible role of the HAE of C. brachiata leaves as herbal antioxidants in the prevention and/ or treatment of oxidative stress-induced diabetes. Results suggested that antioxidant plant phenolics/ flavonoids might be responsible for the antidiabetic efficacy of HAE. Further research can be undertaken on the HAE of C. brachiata leaves for exploration of biochemical mechanisms of antidiabetic action with the isolation of bioactive flavonoids having antidiabetic potential

DIURETIC POTENTIAL OF AERVA LANATA AND ECBOLIUM LIGUSTRINUM ROOT EXTRACTS

Based on the ethnobotanical importance as diuretics Aerva lanata and Ecbolium ligustrinum were selected for presentscreening. Experiment was carried out on male wister strain albino rats using furosemide as standard drug. 20mg/kg and200mg/kg oral doses are selected for standard and test respectively. For quantifying the diuretic activity the urine output,urine pH, sodium, potassium and chloride levels in the urine are measured. The diuretic index value of Ecbolium ligustrinumis 1.70 and nearer to the standard furosemide value 1.80. Aerva lanata group shows less diuretic index of 1.49 compared tostandard. The ratio of the concentration of sodium ions to the potassium ions in control group was found to be 1.39 and theratio for standard, Aerva lanata and Ecbolium ligustrinum are 1.78, 1.49 and 1.68 respectively. Ecbolium ligustrinumaffected the amount of urine excreted and also the electrolyte concentration in urine. The present study concluded that rootsof Aerva lanata and Ecbolium ligustrinum are having diuretic nature

<em>Capsicum</em>: Chemistry and Medicinal Properties of Indigenous Indian Varieties

Capsicum pods (or chili pepper) constitute the world’s second most consumed vegetable crop and spice after tomato in our daily culinary practice. Five indigenous species that are widely domesticated in various parts of India include Capsicum annuum L., Capsicum chinense Jacq., Capsicum frutescens L., Capsicum baccatum L., and Capsicum pubescens L. The chili pods of C. chinense Jacq (locally known as Bhut Jolokia in the Assam state of India) was officially recognized as the world’s hottest Capsicum variety according to the Guinness Book of World Records. Capsaicinoids, a group of chemical principles present in matured capsicum pods, are responsible for the pungency as well as pharmacological/medicinal properties of capsicum. Some important capsaicinoids include capsaicin, followed by dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin. Traditional practices of capsicum pods of Bhut Jolokia have been well documented for the management of various human disorders/ailments, particularly in the north-eastern region of India. In modern medicine, Bhut Jolokia pods have been used in the treatment of arthritis, gastritis, toothache, and musculoskeletal and neuropathic pain including other pharmacological disorders and microbial infections. Capsaicinoids have been reported to exhibit a diverse range of biological effectiveness such as antioxidant, analgesic, and anti-inflammatory, anticarcinogenic effects

Development of Phytomedicines as Novel Antimalarial Lead Molecules: Progress towards Successful Antimalarial Drug Discovery

Among numerous life-threatening infectious diseases (HIV/AIDS, TB, NTDs and EIDs), malaria continues to be the deadliest parasitic disease caused by Plasmodium protozoa transmitted by an infective female Anopheles mosquito. Plasmodium falciparum, the potentially fatal malaria parasite, is believed to be responsible for most of the morbidities and mortalities associated with malaria infections. Artemisinin-based Combination Therapies (ACTs) are currently considered to be the frontline therapy against malaria caused by P. falciparum. Despite significant progresses in antimalarial drug discovery, the control and prevention of malaria is still a challenging task. It is primarily because of the reduced clinical efficacy of existing antimalarial therapies including ACTs due to the widespread emergence of drug-resistant strains of malaria parasites, especially P. falciparum. It is, therefore, necessary to discover and develop novel drug candidates and/or alternative therapies for the treatment as well as prevention of resistant malaria. In this chapter, the potential of phytomedicines as natural sources of novel antimalarial lead molecules/ drugs with recent advances in phytomedicine-based antimalarial drug discovery has been reviewed

Antidiabetic activity of Carallia brachiata Lour. leaves hydro-alcoholic extract (HAE) with antioxidant potential in diabetic rats

Ethnomedicinal surveys have documented the traditional use of Carallia brachiata (Lour.) Merill (Rhizophoraceae) leaves in the management of diabetes mellitus in the Northeastern region of India. This study screens the hydro-alcoholic extract (HAE) of C. brachiata leaves for antioxidant and antidiabetic activities. The HAE was prepared using ethanol:water (7:3) by cold maceration method. The antidiabetic activity of HAE was evaluated in vivo in streptozotocin-induced diabetic rats at the doses of 250 or 500 mg/kg body weight for 21 days. The extract was also evaluated for in vitro and in vivo antioxidant activity. Results revealed that HAE of C. brachiata leaves possesses good hypoglycemic activity in diabetic rats. The hypoglycemic activity of HAE was found significant as compared to normal rats. Results of antioxidant activity were found statistically significant compared to standard drugs, quercetin and gallic acid. Results indicated a possible role of the HAE of C. brachiata leaves as herbal antioxidants in the prevention and/ or treatment of oxidative stress-induced diabetes. Results suggested that antioxidant plant phenolics/ flavonoids might be responsible for the antidiabetic efficacy of HAE. Further research can be undertaken on the HAE of C. brachiata leaves for exploration of biochemical mechanisms of antidiabetic action with the isolation of bioactive flavonoids having antidiabetic potential

Drug Repurposing (DR): An Emerging Approach in Drug Discovery

Drug repurposing (DR) (also known as drug repositioning) is a process of identifying new therapeutic use(s) for old/existing/available drugs. It is an effective strategy in discovering or developing drug molecules with new pharmacological/therapeutic indications. In recent years, many pharmaceutical companies are developing new drugs with the discovery of novel biological targets by applying the drug repositioning strategy in drug discovery and development program. This strategy is highly efficient, time saving, low-cost and minimum risk of failure. It maximizes the therapeutic value of a drug and consequently increases the success rate. Thus, drug repositioning is an effective alternative approach to traditional drug discovery process. Finding new molecular entities (NME) by traditional or de novo approach of drug discovery is a lengthy, time consuming and expensive venture. Drug repositioning utilizes the combined efforts of activity-based or experimental and in silico-based or computational approaches to develop/identify the new uses of drug molecules on a rational basis. It is, therefore, believed to be an emerging strategy where existing medicines, having already been tested safe in humans, are redirected based on a valid target molecule to combat particularly, rare, difficult-to-treat diseases and neglected diseases

Capsaicinoids Content of Some Indigenous Capsicum Varieties of Assam, India

Seven indigenous varieties of capsicum belonging to five different species available locally in Assam were collected and evaluated for capsaicinoids content with a view to assess their relative potency and/or hotness in order to ensure the functional as well as the nutritional quality of capsicum. These include Capsicum annum (Jati Jolokia), Capsicum baccatum (Ohm Jolokia), Capsicum chinense (Bhut Jolokia), Capsicum frutescens (Dhan Jolokia, Maam Jolokia, Totta Bias) and Capsicum pubescens (Bhikue Jolokia). The word Jolokia usually refers to the vernacular (Assamese) name of capsicum or chilli that is often used just after the particular local name of the capsicum variety as mentioned above by the local people of Assam. Results indicate that Bhut Jolokia (Capsicum chinense) and Dhan Jolokia (Capsicum frutescens) possess comparatively higher amount of capsaicinoids (&gt;2%) than other varieties of capsicum. The capsaicinoids content of Bhut Jolokia (2.45%) was still higher than that of Dhan Jolokia (2.14%). Different varieties of capsicum with decreasing order of their capsaicinoids content are as follows: Bhut Jolokia (2.45%) &gt; Dhan Jolokia (2.14%) &gt; Maam Jolokia (1.38%) &gt; Bhikue Jolokia (0.92) &gt; Ohm Jolokia (0.67%) &gt; Jati Jolokia (0.51%) &gt; Totta bias (0.25%). It is very interesting that in addition to Bhut Jolokia, the hottest capsicum of the world, another potential and hot capsicum variety i.e., Dhan Jolokia has been evolved. However, our present study was an attempt to identify such potential and hot capsicum varieties available locally in Assam for the production of capsaicinoids at large in order to meet the increasing demand of capsicum or capsaicinoids in the global market. Furthermore, large scale cultivation and proper utilization of these indigenous capsicum varieties will help improve the agricultural economy of the state and the country as a whole. Keywords: indigenous, Bhut Jolokia, Dhan Jolokia, capsaicioids, climatic condition, capsaici

In vitro antimitotic activity and in silico study of some 6-fluoro-triazolo-benzothiazole analogues

In this work, nine 6-fluoro-triazolo-benzothiazole derivatives were prepared and evaluated for in vitro antimitotic activity. In addition, in silico study was also done using tubulin protein (PDB: 6QQN) by molecular docking method. Results revealed that TZ2 and TZ9 were the most active compounds with antimitotic action opposing the standard drug, aspirin. Results of molecular docking exhibited the inhibitory potential of triazolo-benzothiazole against tubulin protein. The mitotic study indicates the efficacy of triazolo-benzothiazole analogues in inhibiting the proliferation of cancer cells either by promoting microtubule formation or affecting microtubules, thereby preventing microtubule breakdown