Central Drug Research Institute Research Articles

A Tris-Aldehyde Porphyrin Synthon: Synthesis and Characterization of 5,10,15-tris-(4’-(4-Formylphenoxy) propoxyphenyl)-20-(4-nitrophenyl)-porphyrin

Click to increase image sizeClick to decrease image size AcknowledgmentsThis work was supported by Department of Biotechnology (Nanobiotechnology) project (Reg. No: BT/PR25024/NER/95/961/2017, dated February 20th, 2019), granted to Devashish Sengupta from the Government of India, Ministry of Science and Technology. We gratefully acknowledge the Sophisticated Analytical Instrument Facility, of the Sophisticated Test & Instrumentation Centre, Kochi, for mass spectral analysis and the Sophisticated Analytical Instrument facility at the Council of Scientific & Industrial Research–Central Drug Research Institute, Lucknow, for 1HNMR.

PHARMA RESEARCH IN INDIA & ROLE OF CSIR LABORATORIES AND SCIENCE EDUCATION IN INDIA

Dear Reader, It is indeed heartening to note that Dr. D. Srinivasa Reddy, who has close research and professional connections with IDMA and other Pharma Associations and has received Awards also from Industry, has joined the Indian Institute of Chemical Technology (IICT), Hyderabad as the new Director. Dr. Srinivasa Reddy continues to hold the charge as Director, Central Drug Research Institute (CDRI) and the CSIR-IIIM (Indian Institute of Integrative Medicine), Jammu. The fact that Dr. Reddy is simultaneously holding charge of two more leading CSIR Laboratories, while being appointed as the Director of IICT, speaks volumes about his research credentials.

Safety Evaluation of a Standardized Dalbergia sissoo Leaf Extract (DSLE)

Pharmacognosy Research,2022,14,2,172-180.DOI:10.5530/pres.14.2.25Published:April 2022Type:Original ArticleAuthors:Tejal Gandhi, Hital Shah, Ritu Trivedi, Amol Deshmukh, and Lal Hingorani Author(s) affiliations:Tejal Gandhi1,*, Hital Shah2, Ritu Trivedi3, Amol Deshmukh4, Lal Hingorani4 1Department of Pharmacology, Anand Pharmacy College, Anand, Gujarat, INDIA. 2Anand Pharmacy College, Anand, Gujarat, INDIA. 3Endocrinology Division Biological South Block, Central Drug Research Institute, Uttar Pradesh, INDIA. 4Pharmanza Herbals Pvt. Ltd., Dharmaj, Gujarat, INDIA. Abstract:Background: Dalbergia sissoo, also known as Indian Rosewood, is a plant known for its medicinal value with the leaves used traditionally for its effect on joint inflammation and joint pain. Recently, Dalbergia sissoo leaves and its derived novel compound Caviunin glycoside (CAFG) was shown to alleviate symptoms and signs of osteoarthritis in a rat model. Objectives: The objective of the study was to investigate potential adverse effects, if any, of a standardized Dalbergia sissoo leaf extract (DSLE) in rats following sub-chronic administration. Materials and Methods: DSLE was standardized to a composition of not less than 2% w/w CAFG and not less than 6% w/w total flavonoids. In the sub-chronic study, Wistar rats (10/sex/group) were administered via gavage 0 (control), 310, 620, 1240 mg/kg body weight/day of DSLE for 90 days. Two additional groups received 0 and 1240mg/kg /day of the extract for 90 days, followed by a 28-day reversal phase. Results: The study revealed that administration of the DSLE did not result in any toxicologically significant treatment related changes in clinical observation, ophthalmic examination, body weight, body weight gain, feed consumption, clinical pathology and organ weight. The haematology and serum chemistry parameters compared to the control group were also within the normal laboratory limits. Terminal necroscopy did not indicate any treatment related gross or histopathological findings. The results of genotoxicity studies as evaluated by gene mutations in Salmonella typhimurium, and in vitro chromosome aberration assay did not reveal any genotoxicity of the extract. Conclusion: Based on the results of this study, the no observed-adverse-effect level (NOAEL) for this standardized Dalbergia sissoo leaf extract was determined as 1240 mg/kg body weight/day, the highest dose tested. Key words: Dalbergia sissoo, Dietary ingredient, Leaf extract, Safety, Toxicity, Sissoo, Bone health. View:PDF (318.13 KB)

First person – Pragya Chandrakar

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Pragya Chandrakar is first author on ‘Jagged–Notch-mediated divergence of immune cell crosstalk maintains the anti-inflammatory response in visceral leishmaniasis’, published in JCS. Pragya conducted the research described in this article while a Senior Research Fellow in Dr Susanta Kar's lab at the CSIR Central Drug Research Institute, Lucknow, India. She is now a Postdoctoral Research Fellow in the lab of Dr John Chan at Albert Einstein College of Medicine, New York, USA, investigating the different possible mechanisms by which foreign pathogens breach the immune system.

Amit Joharapurkar wins industrial scientist award

Amit Joharapurkar, a general manager at Zydus Cadila in Ahmadabad, India, is the winner of the 2019 Indian Society of Chemists and Biologists Award of Appreciation for Industrial Scientists. Joharapurkar’s research is in the area of small-molecule drug discovery, which includes the development of prolyl hydroxylase inhibitor Desidustat. He has contributed to the discovery and development of new chemical entities at Zydus Cadila and has been actively involved in the development of seven new investigational drugs. He is also the recipient of 2018 Central Drug Research Institute Award for Excellence in Drug Research. Please send announcements of awards to l_wang@acs.org.

Scoping review to map evidence on mechanism of action, pharmacokinetics, effectiveness and side effects of centchroman as a contraceptive pill

ObjectiveTo systematically identify and map the available evidence on effectiveness, side effects, pharmacokinetics and mechanism of action of centchroman as a contraceptive pill.IntroductionCentchroman was introduced in the Indian national family...

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

Evaluation of the impact of 16-dehydropregnenolone on the activity and expression of rat hepatic cytochrome P450 enzymes

16-dehydropregnenolone (DHP) is a promising novel antihyperlipidemic agent developed and patented by Central Drug Research Institute (CDRI), India. The purpose of the present study was to investigate whether DHP influences the activities and mRNA expression of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, CYP2D2, CYP2E1 and CYP3A1) in Sprague-Dawley (SD) rats. A cocktail suspension of CYP probe substrates which contained caffeine (CYP1A2), tolbutamide (CYP2C11), dextromethorphan (CYP2D2), chlorzoxazone (CYP2E1) and dapsone (CYP3A1) was administered orally on eighth- or fifteenth-day to rats pre-treated with DHP intragastrically at a dose of 36 and 72mg/kg for one week and two weeks. The concentrations of probe drugs in plasma were estimated by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Alongside, the effect of DHP on CYPs activity and mRNA expression levels were assayed in isolated rat liver microsomes and by real-time reverse transcription-polymerase chain reaction (RT-PCR), respectively. DHP had significant inducing effects on CYP1A2, 2C11, 2D2 and 2E1 with no effect on CYP3A1 in dose- and time-dependent manner, as revealed from the pharmacokinetic profiles of the probe drugs in rats. In-vitro microsomal activities and mRNA expression results were in good agreement with the in-vivo pharmacokinetic results. Collectively, the results unveiled that DHP is an inducer of rat hepatic CYP enzymes. Hence, intense attention should be paid when DHP is co-administered with drugs metabolized by CYP1A2, 2C11, 2D2 and 2E1, which might result in drug-drug interactions and therapeutic failure.

Determination of metabolic profile of novel triethylamine containing thiophene S006-830 in rat, rabbit, dog and human liver microsomes.

CDRI S006-830 is a potent triethylamine containing thiophene antitubercular compound of the Central Drug Research Institute, India. The present study aimed to conduct comprehensive metabolic investigations of CDRI S006-830 to corroborate its preclinical investigations. Preliminary metabolic investigations were performed to assess the metabolic stability, enzyme kinetics, reaction phenotyping, and metabolite identification of CDRI S006-830 in rat, rabbit, dog, and human liver microsomes using liquid chromatography with mass spectrometry. The observed in vitro t1/2 and Clint values were 9.9 ± 1.29, 4.5 ± 0.52, 4.5 ± 0.86, 17 ± 5.21 min and 69.60 ± 8.37, 152.0 ± 17.26, 152.34 ± 27.63, 33.62 ± 21.04 μL/min/mg in rat, rabbit, dog and human liver microsomes respectively. These observations suggested that CDRI S006-830 rapidly metabolized in the presence of NADPH in liver microsomes of rat, rabbit and dog while moderately metabolized in human liver microsomes. It was observed that CDRI S006-830 exhibited monophasic Michaelis-Menten kinetics. The metabolism of CDRI S006-830 was primarily mediated by CYP3A4 and was deduced by CYP reaction phenotyping with known potent inhibitors. CYP3A4 involvement was also confirmed by cDNA-expressed recombinant human isozyme activity with different CYPs. Four major phase-I metabolites of S006-830, (M-1 to M-4) were detected in rat, rabbit, dog (except M4) and human liver microsomes.

Determination of metabolic profile of novel triethylamine containing thiophene S006-830 in rat, rabbit, dog and human liver microsomes.

CDRI S006-830 is a potent triethylamine containing thiophene antitubercular compound of the Central Drug Research Institute, India. The present study aimed to conduct comprehensive metabolic investigations of CDRI S006-830 to corroborate its preclinical investigations. Preliminary metabolic investigations were performed to assess the metabolic stability, enzyme kinetics, reaction phenotyping, and metabolite identification of CDRI S006-830 in rat, rabbit, dog, and human liver microsomes using liquid chromatography with mass spectrometry. The observed in vitro t1/2 and Clint values were 9.9 ± 1.29, 4.5 ± 0.52, 4.5 ± 0.86, 17 ± 5.21 min and 69.60 ± 8.37, 152.0 ± 17.26, 152.34 ± 27.63, 33.62 ± 21.04 μL/min/mg in rat, rabbit, dog and human liver microsomes respectively. These observations suggested that CDRI S006-830 rapidly metabolized in the presence of NADPH in liver microsomes of rat, rabbit and dog while moderately metabolized in human liver microsomes. It was observed that CDRI S006-830 exhibited monophasic Michaelis-Menten kinetics. The metabolism of CDRI S006-830 was primarily mediated by CYP3A4 and was deduced by CYP reaction phenotyping with known potent inhibitors. CYP3A4 involvement was also confirmed by cDNA-expressed recombinant human isozyme activity with different CYPs. Four major phase-I metabolites of S006-830, (M-1 to M-4) were detected in rat, rabbit, dog (except M4) and human liver microsomes.

Mechanisms, Efficacy, and Safety ofBacopa monnieri(Brahmi) for Cognitive and Brain Enhancement

The plant Bacopa monnieri (water hyssop, Brahmi, thyme-leaved Gratiola, herb of grace, and Indian pennywort) is a perennial, creeping herb native to the wet lands of India, particularly northeast and southern regions. Bacopa is an important plant of Ayurveda, where it is named as Brahmi, after Lord Brahma, the mythological creator of the world and originator of the science of Ayurveda. Bacopa is frequently mentioned in the religious, social, and medical treatises of India since the time of Vedic civilization. Its antiquity can be traced to the time of Athar Ved (the science of well-being) written in 800 BC where Bacopa finds a mention in the very first verse of the third chapter of Athar Samhita (compilation on the factors promoting well-being). More recently researchers have turned their attention to better understanding the mechanisms and efficacy of various extracts of Bacopa monnieri on human conditions. Although extracts of Bacopa have been studied and used to treat various disorders for centuries (pain, epilepsy, and inflammation, amongst many) perhaps the chief therapeutic claim concerning its benefits has been in improving memory. The Indian government has invested significant resources and conducted hundreds of studies examining the mechanisms of action on the brain and at a cellular level. Interestingly this research has uncovered a myriad of possible mechanisms relating to anti-inflammatory, antioxidant, metal chelation, amyloid, and cholinergic effects amongst many others. Although it is not unusual for plant based medicines to have multiple effects on cellular processes, Bacopa monnieri is perhaps one of the most scientifically studied in terms of mechanisms of action. Interestingly these mechanisms seem to comprehensively map on to the biological mechanisms that many researchers have argued underpin cognitive and memory processes. In 1996 a special extract of Bacopa monnieri was launched by the Indian Government's Central Drug Research Institute, Lucknow, termed CDRI 08. It was thought at the time that this particular standardised extract had been subjected to the most research and was the most promising extract for medical conditions. In 2010 the three editors for this special issue attended CDRI's 60th research anniversary where a special one-day symposium on research on CDRI 08 was held. It is this extract of Bacopa monnieri that is the focus of most of the papers in this special issue which reports studies relating to the safety, mechanisms, and efficacy of specific extracts of Bacopa monnieri. Over the last ten years there have been growing scientific studies on this interesting terrestrial herb. As can be seen in Figure 1 the number of publications concerning Bacopa monnieri is steadily growing reflecting increasing scientific interest in this plant for human conditions. Most of these studies reflect scientific endeavours relating to cellular mechanisms. As such these studies are an excellent base to launch larger clinical trials in humans. Although much is known about the mechanisms of Bacopa extracts on the brain there are still significant gaps in our knowledge. For instance, long-term chronic trials in older people are now required to understand whether Bacopa extracts such as CDRI 08 can prevent age-related cognitive decline or even more insidious diseases such as Alzheimer's dementia. We note that a number of studies are also currently examining the effect of Bacopa extracts on improving cognitive and behavioural function in younger people. Clearly the next decade will focus on larger clinical trials in humans and expand upon the excellent animal and preclinical work mainly conducted in India. Figure 1 Con Stough Hemant Singh Andrea Zangara

Assay method for quality control and stability studies of a new anti-diabetic and anti-dyslipidemic flavone (S002-853).

Background:Flavonoid-rich extract of the plant is long known for its anti-diabetic activities in traditional medicine. S002-853, a new flavone derivative synthesized by Central Drug Research Institute (CDRI) has been used for the present study.Objectives:The present study aimed at development of an assay method for quality control (QC) and stability studies of a new anti-diabetic and anti-dyslipidemic agent CDRI compound S002-853.Materials and Methods:A validated high-performance liquid chromatography analysis method for S002-853 was developed for in process QC and stability studies. The separation was achieved on a RP-C18 (25 cm × 0.4 cm, 5 μm, Phenomenex) at 240 nm with flow rate of 1.0 ml/min. This method was applied successfully in establishing forced degradation and drug-excipient testing protocols as per International Conference on Harmonization guidelines.Results:The result of estimation and stress testing studies indicated a high degree of selectivity of this method. S002-853 was most stable at pH 7 and under photolytic conditions. The temperature degradation pattern of S002-853 was found to follow the zero order degradation.Conclusion:The method described is easy and simple hence can be easily reproduced. This method can be very useful for bulk manufacture QC, and drug development process.

Pharmacokinetic study and bioavailability of a novel synthetic trioxane antimalarial compound 97/63 in rats.

Single dose pharmacokinetics study of 97/63 (IND191710, 2004), a trioxane antimalarial developed by Central Drug Research Institute, Lucknow, India, was studied in rats following intravenous and oral administration. Serum samples were analysed by HPLC-UV assay. Separation was achieved on a RP-18 column attached with a guard using acetonitrile : phosphate buffer (70 : 30% v/v) with UV detector at wavelength 244 nm. Serum samples were extracted with n-hexane. Two-compartment model without lag time and first-order elimination rate was considered to be the best fit to explain the generated oral and intravenous data. Method was sensitive with limit of quantification of 10 ng mL−1. Recovery was >74%. Terminal half-life and area under curve (AUC) after administering single oral (72 mg kg−1) and intravenous (18 mg kg−1) doses were 10.61 h, 10.57 h, and 1268.97 ng h mL−1, 2025.75 ng h mL−1, respectively. After oral dose, 97/63 was rapidly absorbed attaining maximum concentration 229.24 ng mL−1 at 1 h. Bioavailability of 97/63 was ~16%. The lower bioavailability of drug may be due to poor solubility and first-pass metabolism and can be improved by prodrug formation of 97/63.

Use of digital resources by the scientists of Central Drug Research Institute (CDRI), India: A survey

The purpose of this study is to find out the level of use of digital resources by the scientists of CDRI, Lucknow (India). As a matter of fact, CDRI is among the thirty eight laboratories that are functioning under the aegis of the Council of Scientific and Industrial Research (CSIR) of India headed by the Prime Minister of the nation as its president. CDRI is a pioneer research organization in the field of biomedical research in India. A well structured questionnaire was administered to the scientists of CDRI, Lucknow (India) to collect data regarding the use of digital resources. The survey reveals that most of the scientists are aware of the availability of digital resources and frequently use them for their research work and paper writing. They fully agree that with the usefulness of digital resources the quality of research work improves with enrichment of appurtenant contents and materials leading to high quality manuscript. It is also observed that majority of scientists of the CDRI keep themselves abreast of developments in digital resources and their proper utilization for their research projects. It is, however, found that slow downloading is the obstacle in proper and full utilization of digital resources.

Role of type-II pathway in apoptotic cell death induction by photosensitized CDRI-97/78 under ambient exposure of UV-B

Novel trioxane 97/78, developed by Central Drug Research Institute (CDRI), Lucknow has shown promising antimalarial activity. Clinical experience of anti-malarial drugs registered the occurrence of phototoxicity in patients exposed with sunlight subsequent to medication. Photodegradation study has identified one photo-product up to 4h under UV-B/Sunlight by LC–MS/MS. UV-B irradiated 97/78 compound produced 1O2 via type-II dependent reaction mechanism, corroborated by its specific quencher. 2′-dGuO degradation and % tail development in photochemical as well as comet test, advocated the genotoxic potential of 97/78. The photocytotoxicity assays (MTT and NRU) on HaCaT cell line revealed the considerable decline in cell viability by 97/78. Cell cycle and Annexin V/PI double stain along with AO/EB demonstrated the G2/M phase arrest and apoptosis. Significant caspase-3 activity was measured in photoexcited 97/78 by colorimetric assay. Fluorescence stain with AO/JC-1 confirmed the lysosomal disruption and mitochondrial membrane destabilization by UV-B irradiated 97/78. Gene expression by RT-PCR showed significant upregulation of p21 and pro-apoptotic Bax, but no change observed in Bcl-2. In conclusion, the study highlights ROS mediated DNA damage, lysosomal and mitochondrial destabilization via upregulation of Bax and activation of caspase-3 which further leads to apoptosis.

Use of digital resources by the scientists of Central Drug Research Institute (CDRI), India: A survey

The purpose of this study is to find out the level of use of digital resources by the scientists of CDRI, Lucknow (India). As a matter of fact, CDRI is among the thirty eight laboratories that are functioning under the aegis of the Council of Scientific and Industrial Research (CSIR) of India headed by the Prime Minister of the nation as its president. CDRI is a pioneer research organization in the field of biomedical research in India. A well structured questionnaire was administered to the scientists of CDRI, Lucknow (India) to collect data regarding the use of digital resources. The survey reveals that most of the scientists are aware of the availability of digital resources and frequently use them for their research work and paper writing. They fully agree that with the usefulness of digital resources the quality of research work improves with enrichment of appurtenant contents and materials leading to high quality manuscript. It is also observed that majority of scientists of the CDRI keep themselves abreast of developments in digital resources and their proper utilization for their research projects. It is, however, found that slow downloading is the obstacle in proper and full utilization of digital resources.

Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol

Leishmania donovani (LD), the causative agent of visceral leishmaniasis (VL), extracts membrane cholesterol from macrophages and disrupts lipid rafts, leading to their inability to stimulate T cells. Restoration of membrane cholesterol by liposomal delivery corrects the above defects and offers protection in infected hamsters. To reinforce further the protective role of cholesterol in VL, mice were either provided a high-cholesterol (atherogenic) diet or underwent statin treatment. Subsequent LD infection showed that an atherogenic diet is associated with protection, whereas hypocholesterolemia due to statin treatment confers susceptibility to the infection. This observation was validated in apolipoprotein E knockout mice (AE) mice that displayed intrinsic hypercholesterolemia with hepatic granuloma, production of host-protective cytokines, and expansion of antileishmanial CD8(+)IFN- γ (+) and CD8(+)IFN- γ (+)TNF- α (+) T cells in contrast to the wild-type C57BL/6 (BL/6) mice when infected with LD. Normal macrophages from AE mice (N-AE-MΦ) showed 3-fold higher membrane cholesterol coupled with increased fluorescence anisotropy (FA) compared with wild-type macrophage (N-BL/6-MΦ). Characterization of in vitro LD-infected AE macrophage (LD-AE-MΦ) revealed intact raft architecture and ability to stimulate T cells, which were compromised in LD-BL/6-MΦ. This study clearly indicates that hypercholesterolemia, induced intrinsically or extrinsically, can control the pathogenesis of VL by modulating immune repertoire in favor of the host.

New Flavones from the Stem Bark of Morus alba L.

Morus alba L. (Moraceae) is a perennial, heterogenous out breeding tree or shrub commonly known as mulberry [1,2]. It is indigenous to China and extensively cultivated throughout Eastern, Central, and Southern Asia. Mulberry is known to have antimicrobial, antioxidant, antidiabetic, neuroprotective, skin tonic, immunonutrition and anticancer activity. The bark of the large stem is brown, rough, fibrous, fissured mostly vertical, and is used as a vermifuge and purgative [3,4]. Mulberrochomene, cyclomulberrochromene, mulberrin, cyclomulberrin, mulberranol, albanol A and B, β-sitosterol, α-amyrin, β-amyrin, phytol and lupeol have been reported from the stem bark [5,6,7]. The present study deals with the isolation of two new flavones characterized as 5,4'-dihydroxy-7-octadec-9-enoxy-8-(ã-methylallyl)-2',3'-(2''', 3'''-dimethylpyr-1'''-enyl) flavone and 5,7,4'-trihydroxy-8-(ã-methylallyl)-2', 3'-(2''', 3'''-dimethylpyr-1'''-enyl) flavone along with the known compounds α-amyrin acetate, β-amyrin-β-D-glucopyranoside and betulinic acid from the alcoholic extract of M. alba stem bark from the Delhi region. The structures of compounds have been established on the basis of FAB-MS, 1D-NMR (1H-NMR, 13C-NMR) and 2D-NMR (1H-1H COSY, HMBC) spectroscopic techniques and chemical reactions. Acknowledgements: The authors are thankful to the Head, SAIF, Central Drug Research Institute, Lucknow, India, for instrumentation facility.

Determination of metabolic profile of anti‐malarial trioxane CDRI 99/411 in rat liver microsomes using HPLC

CDRI 99/411 is a potent 1,2,4-trioxane anti-malarial candidate compound of the Central Drug Research Institute, India. This study aimed to conduct comprehensive in vitro metabolic investigations of CDRI 99/411 to corroborate its preclinical investigations. Preliminary in vitro metabolic investigations were performed to assess the metabolic stability [in vitro half-life (t(1/2) ) and in vitro hepatic intrinsic clearance (Cl(int) )] of CDRI 99/411 in male Sprague-Dawley rat and human liver microsomes using validated high-performance liquid chromatography with photodiode array detector. The observed in vitro t(1/2) of the compound in rat and human liver microsomes was 13 min with in vitro Cl(int) 130.7±25.0 μL/min/mg and 19 min with in vitro Cl(int) 89.3 ± 17.40 μL/min/mg. These observations suggested moderate metabolic degradation and in vitro Cl(int) with insignificant difference (p>0.05) in the metabolic stability profile in rat and human. Hence, in vitro metabolic investigations were performed with rat liver microsomes. It was observed that CDRI 99/411 exhibited sigmoidal kinetics. At nonlinear regression (r ≥ 0.99) EC(50) and Hill slope values were 17 µm and 1.50, respectively. The metabolism of CDRI 99/411 was primarily mediated by CYP3A2 and was inferred by CYP reaction phenotyping with known potent inhibitors. Two metabolites of CDRI 99/411 were detected which were undetectable on incubation with 1-aminobenzotriazole and ketoconazole.

Young Investigator: Wahajuddin

Supervisor’s supporting comments Wahajuddin has shown strong enthusiasm with equal intensity of hard work in bioanalytical research since the day he joined as a scientist in this department. His intrinsic learning abilities made him acquire deep knowledge in the area of bioanalysis and he quickly became competent in conducting regulatory/exploratory studies in pharmacokinetics, biopharmaceutics and drug metabolism – harnessing the strengths of bioanalysis. Due to his skills and knowledge in advanced pharmaceutical analysis tools and techniques, he has also been given the responsibility to work as course coordinator for MS (Pharm.) Pharmaceutics at the newly established National Institute of Pharmaceutical Education and Research, which is an institute of national importance under the aegis of the Ministry of Chemicals and Fertilizers, Government of India. Through our Young Knowledge Promotion Initiative and Young Leadership Promotion Initiative, Wahajuddin was given the responsibility of being the corresponding author and first co-author in the majority of papers that have been published by our group, since he was instrumental in generating ideas, planning and executing the studies, compiling and analyzing the data and in writing and communicating the manuscripts. This enabled him to publish very good work in journals such as the Journal of Chromatography B, the Journal of Separation Science, Food & Chemical Toxicology, the Journal of Nutritional Biochemistry and Menopause within a very short period. Many other manuscripts are at various stages of communication and publication. His contribution also resulted in filing a patent application from the Central Drug Research Institute in 2007 (patent No.: #0081NF2007). He has also presented his work at many international conferences, symposia and seminars. He recently presented his work at the International Pharmaceutical Federation Pharmaceutical Science World Congress 2010 in association with American Association of Pharmaceutical Scientists Annual Exposition 2010 held on 14–18 November 2010 in New Orleans, USA. I am sure that he will achieve even greater feats in times to come and strongly recommend his candidature for Bioanalysis: Young Investigator 2011. Nominated by: Girish Kumar Jain, Deputy Director & Head, Division of Pharmacokinetics & Metabolism, Central Drug Research Institute, CSIR, Lucknow, India. gk_jain@cdri.res.in