Dr. Mohd Kamil Hussain, PhD - Govt. Raza Post Graduate College Rampur - Assitant Professor

Dr. Mohd Kamil Hussain

PhD

Govt. Raza Post Graduate College Rampur

Assitant Professor

Rampur, U.P. India | India

Main Specialties: Chemistry

ORCID logohttps://orcid.org/0000-0002-2915-8106


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Dr. Mohd Kamil Hussain, PhD - Govt. Raza Post Graduate College Rampur - Assitant Professor

Dr. Mohd Kamil Hussain

PhD

Introduction

Dr. Hussain received his doctorate from Central Drug Research Institute-Jawaharlal Nehru University in the area of breast cancer, specifically the development of new anti-cancer agents. He is an assistant professor at Govt. Raza Post Graduate College Rampur, where he is engaged in developing DNA ligase inhibitors and anti-cancer agents.

Primary Affiliation: Govt. Raza Post Graduate College Rampur - Rampur, U.P. India , India

Specialties:

Research Interests:


View Dr. Mohd Kamil Hussain’s Resume / CV

Education

Mar 2014
CSIR-Central Drug Research Institute Lucknow
Ph.D
Organic Synthesis and medicnanl Chemistry
Jul 2007
CCS University Meerut
M.Sc
Chemistry
Jul 2004
CCS University Meerut
B.Sc
Chemistry, Zoology, Botany
May 1999
Board of High School and Intermediate U.P
Intermediate
May 1997
Board of High School and Intermediate U.P
High School
CSIR-Central Drug Research Institute Medicinal and Process Chemistry Division
Ph.D.
Medicinal and Process ChemistrChemistryy Division

Experience

Feb 2015
Incentive award
Paper published in Organic Letters
Jul 2010
Senior Research Fellowship
Senior Research Fellow
Dec 2008
Junior Research Fellowship (JRF)
Junior Research Fellow
Dec 2008
Graduate Aptitude Test in Chemistry (GATE
Sep 2015
Govt. Raza Post Graduate College
Assistant Professor
Department of Chemistry

Publications

17Publications

67Reads

84Profile Views

and antidiabetic effect of extracts of , and .

Integr Med Res 2018 Jun 27;7(2):176-183. Epub 2018 Mar 27.

Department of Chemistry, HNB Garhwal University, Srinagar, India.

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http://dx.doi.org/10.1016/j.imr.2018.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026355PMC
June 2018
45 Reads

Dithiolethiones: a privileged pharmacophore for anticancer therapy and chemoprevention.

Future Med Chem 2018 05 11;10(10):1241-1260. Epub 2018 May 11.

Department of Chemistry, Govt. Raza PG College, Rampur, Uttar Pradesh 244901, India.

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http://dx.doi.org/10.4155/fmc-2017-0281DOI Listing
May 2018
3 Reads
4.000 Impact Factor

Identification of a novel human DNA ligase I inhibitor that promotes cellular apoptosis in DLD-1 cells: an in silico and in vitro mechanistic study

RSC Adv., 2016, Sept 23; 6, 94574–94587

RSC Advances

The processes of DNA replication and repair are accomplished by the concerted action of several proteins. Among them human DNA ligases play an important role during the last step of almost all DNA replication and repair processes, where they seal the nicks between DNA strands. In humans, three kinds of DNA ligases (human DNA ligase I, III, IV) are found. DNA ligase I (hLigI) is involved in both DNA replication as well as in DNA repair pathways and is reported to be over-expressed in rapidly dividing cells, including cancer cells. For this reason, in this study we have targeted hLigI for studying its response as a novel anticancer target. We have screened for ligase I inhibitors from our in-house small molecule library by a previously validated pharmacophore based virtual screening method and found a novel hLigI inhibitor. This compound (S-097/98) demonstrated antiproliferative activities specifically in DLD-1 (colon), MDAMB- 231 (triple negative breast) and HepG2 (liver) cancer cell lines at low micromolar concentrations of 6–7 mM. Mechanistic studies show that the compound can directly interacts with the hLigI protein and inhibits ligation of both the purified protein in vitro, as well as in cell lysate of DLD-1 cells treated with the inhibitor. The compound also arrests cell cycle progression at the G2/M phase and increases the nuclear size of DLD-1 cancer cells, thereby demonstrating its antiproliferative activity. Finally, the compound promotes cellular apoptosis in DLD-1 cells.

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September 2016
1 Read

Discovery of 3,4,6-Triaryl-2-pyridones as Potential Anticancer Agents that Promote ROS-Independent Mitochondrial-Mediated Apoptosis in Human Breast Carcinoma Cells

Chemistry Select, 2016 Sept1; 1(14): 4255

Chemistry Select

A library of 3,4,6-triaryl-2-pyridones has been synthesized using multicomponent reaction (MCR) of substituted acetophenones, benzaldehydes and phenyl acetamides. All the synthesized compounds were evaluated for their anti-breast cancer activity, in vitro in ER+ and ER- cancer cell lines, wherein, compounds 11 (4-(3,4-dimethoxyphenyl)-6-(4-methoxyphenyl)-3-phenylpyridin-2(1H)-one) and 35 (3,6-bis(4-methoxyphenyl)-4-(4-(2-(piperidin-1-yl) ethoxy)phenyl)pyridin-2(1H)-one) were found to be the most active with best safety profile towards non-cancer originated HEK-293 cells. Cell cycle analysis showed that the compounds 11 and 35 induced statistically significant arrest of cells in G1 phase and reduction in S-phase cells in a dose-dependent manner. Compound 11, unlike compound 35 exerts breast cancer cell membrane specific action as observed with LDH assay, whereas compound 35 induced ROS-independent mitochondrial-mediated apoptosis in breast cancer cell line, MDA-MB-231. Apoptotic activity of compound 35 was also confirmed by DNA fragmentation and by expression of pro-apoptotic genes, BAD, BAK, and BimL. Compound 35 is about five times safer than its effective IC50 values in MDA-MB-231 cell line, which makes it a non-toxic breast cancer therapeutic agent.

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September 2016
1 Read

Synthesis of targeted dibenzo[b,f]thiepines and dibenzo[b,f]oxepines as potential lead molecules with promising anti-breast cancer activity.

Eur J Med Chem 2015 Jun 27;99:113-24. Epub 2015 May 27.

Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Uttar Pradesh, Lucknow 226031, India. Electronic address:

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http://dx.doi.org/10.1016/j.ejmech.2015.05.035DOI Listing
June 2015
8 Reads
3.450 Impact Factor

Inhibitory effect of 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran (K-1) on human primary endometrial hyperplasial cells mediated via combined suppression of Wnt/β-catenin signaling and PI3K/Akt survival pathway

Cell Death & Disease (2014) 5, e1380; doi:10.1038/cddis.2014.334

Cell Death & Disease

Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women. Apart from estrogenic induction, aberrant activation of the Wnt/β-catenin signal is well known to correlate with endometrial hyperplasia and its carcinoma. The benzopyran compound 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo (b) pyran(K-1), a potent antiestrogenic agent, has been shown to have apoptosis-inducing activity in rat uterine hyperplasia. The current study was undertaken to explore the effect of the benzopyran compound K-1 on growth and Wnt signaling in human endometrial hyperplasial cells. Primary culture of atypical endometrial hyperplasial cells was characterized by the epithelial cell marker cytokeratin-7. Results revealed that compound K-1 reduced the viability of primary endometrial hyperplasial cells and expression of ERα, PR, PCNA, Wnt7a, FZD6, pGsk3β and β-catenin without affecting the growth of the primary culture of normal endometrial cells. The β-catenin target genes CyclinD1 and c-myc were also found to be reduced, whereas the expression of axin2 and Wnt/β-catenin signaling inhibitor Dkk-1 was found to be upregulated, which caused the reduced interaction of Wnt7a and FZD6. Nuclear accumulation of β-catenin was found to be decreased by compound K-1. K-1 also suppressed the pPI3K/pAkt survival pathway and induced the cleavage of caspases and PARP, thus subsequently causing the apoptosis of endometrial hyperplasial cells. In conclusion, compound K-1 suppressed the growth of human primary endometrial hyperplasial cells through discontinued Wnt/β-catenin signaling and induced apoptosis via inhibiting the PI3K/Akt survival pathway.

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June 2014
5 Reads

Metal-Free Tandem Approach to Structurally Diverse N-Heterocycles: Synthesis of 1,2,4- Oxadiazoles and Pyrimidinones

New J. Chem., 2014,38, 3062-3070

New Journal of Chemistry

A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2,4-oxadiazoles and 2,6 disubstituted pyrimidin-4-ones is described via carboxamidation of amidines with aryl carboxylic acids and aryl propargylic acids. The reactions occur at room temperature forming N-acylamidines which undergo tandem nucleophilic addition–deamination–intramolecular cyclisation to give the corresponding heterocyclic compounds in good to excellent yields. This one pot approach has led to the successful synthesis of the drug lead molecule, ataluren, 3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl) benzoic acid in two steps

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April 2014
6 Reads

Tandem C-2 functionalization-intramolecular azide-alkyne 1,3-dipolar cycloaddition reaction: a convenient route to highly diversified 9H-benzo[b]pyrrolo[1,2-g][1,2,3]triazolo[1,5-d][1,4]diazepines.

Org Lett 2014 Jan 18;16(2):560-3. Epub 2013 Dec 18.

Medicinal and Process Chemistry Division and §Molecular and Structural Biology Division, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road Lucknow 226031, India.

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http://dx.doi.org/10.1021/ol403420zDOI Listing
January 2014
11 Reads

Benzopyran derivative CDRI-85/287 induces G2-M arrest in in estrogen receptor-positive breast cancer cells via modulation of estrogen receptor α and β signaling, in parallel to EGFR signaling and suppresses the growth of tumor xenograft

Steroid, 2013, 78, 1071

Steroid

In an endeavor to develop novel and improved selective estrogen receptor modulators as anti-breast cancer agents, the benzopyran compounds have been synthesized and identified which act as potent anti-estrogen at uterine level. The present study evaluates the anti-tumor activity of 2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzo(b)pyran (CDRI-85/287) and explores the mechanism of action with a view to describe its potential to inhibit proliferation in ER-positive breast cancer cells MCF-7 and T47D. The compound decreased the expression of ERα while increased the expression of ERβ thereby altering ERα/ERβ ratio in both cell lines. Although the compound showed low binding affinity to ERs, it acted as ERα antagonist and ERβ agonist in decreasing ERE- or AP-1-mediated transcriptional activation in these cells. Transactivation studies in ERα/β-transfected MDA-MB231 cells suggested that at cyclin D1 promoter, compound antagonized the action of ERα-mediated E2 response while acted as estrogen agonist via ERβ. Further, the compound led to decreased expression of ERα-dependent proliferation markers and ERβ-dependent cell cycle progression markers. The expression of cell cycle inhibitory protein p21 was increased leading to G2/M phase arrest. In parallel, compound also interfered with EGFR activation, caused inhibition of PI-3-K/Akt pathway and subsequent induction of apoptosis via intrinsic pathway. A significant reduction in tumor mass and volume was observed in 85/287-treated mice bearing MCF-7 xenograft. We conclude that compound 85/287 exhibits significant anti-tumor activity via modulation of genomic as well as non-genomic mechanisms involved in cellular growth and arrested the cells in G2 phase in both MCF-7 and T47D breast cancer cells. Study suggests that CDRI-85/287 may have therapeutic potential in ER-positive breast cancer.

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November 2013
1 Read

The anti-proliferative effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b) pyran ispotentiated via induction of estrogen receptor beta and p21 in humanendometrial adenocarcinoma cells

Journal of Steroid Biochemistry & Molecular Biology

In an effort to develop novel therapeutic agents for endometrial cancer, benzopyran derivatives synthesized at our institute display significant inhibitory activity on cellular growth in uterine cancer cells. The current study was undertaken to demonstrate and explore the estrogen receptor (ER) subtype mediated mechanism of action of benzopyran derivative 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b) pyran (K-1) in human endometrial cancer cells. K-1 competitively inhibited the estradiol binding to human ERα and ERβ and showed growth inhibitory activity in human endometrial Ishikawa, HEC1B and primary endometrial adenocarcinoma cells. Transient transactivation assays carried out in COS-1 cells have demonstrated the diminished ERα-ERE mediated- and induced the ERβ-ERE mediated-transactivation triggered by compound. It also induced ER-mediated transactivation of the cyclin-dependent kinase inhibitor (CDKI) p21WAF-1 in both COS-1 cells and in Ishikawa cells. ERβ inducing effects of compound were blocked by ICI182,780. In endometrial adenocarcinoma cells, it induced ERβ and p21 expression significantly whereas the expression of fos, jun and ERα were significantly reduced. In addition, compound promoted ERα–β heterodimerization as observed in Ishikawa cells. These results demonstrate that the benzopyran compound suppressed the cellular growth via ERβ agonism, induction of p21 and via promoting the ERα–β heterodimerization, in addition to its antagonistic effects exerted on ERα, in human endometrial cancer cells. The study suggests that the dual action of benzopyran molecule may be of significant therapeutic value in ERα/β-positive cases of endometrial cancer.

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November 2013
2 Reads

Design and Synthesis of ERα / ERβ Selective Coumarin and Chromene Derivatives as Potential Anti-Breast Cancer and Anti-Osteoporotic Agents

RSC Adv., 2014,4, 8828-8845

RSC Advances

Several new coumarin and chromene prototype derivatives have been synthesised and evaluated for their ERα and ERβ selective activity. Coumarin prototype compounds 18 & 19 were found to be ERα selective and the most active, exhibiting potential antiproliferative activity against both ER +ve & ER −ve breast cancer cell lines. The surprise finding of the series, however, are the novel prototype III chromenes 45 & 46, with aroyl substitution at the 6th position. Both the compounds have shown potent antiproliferative activity against both the breast cancer cell lines, promote alkaline phosphatase activity, enhance osteoblast mineralization in vitro, significantly decrease ERE–ERα dependent transactivation and induce ERβ activity. This specific upregulation of ERβ isoform activity of compound 45 may be responsible for the antiosteoporotic activity at picomolar concentration. In addition, both the compounds were also devoid of any estrogenic activity, which correlates to their antiestrogenic behaviour in the two breast cancer cell lines. Assessment of selectivity using specific SiRNAs for ERα and ERβ revealed that most of the compounds showed ERα and ERβ-mediated action, except compound 28, which showed selectivity to ERα only. Computational docking analysis of active compounds 18 and 45 was conducted to correlate the interaction with the two receptors and it was found that the docked conformations of the coumarin prototype, compound 18 at ERα and ERβ active sites were more or less superimposable on each other. However, the unique orientation of the aminoalkoxy side chain of novel chromene (prototype III) compound 45 in the ERβ binding cavity may be responsible for its potential biological response.

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November 2013
1 Read

Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran: Evidence for involvement of GPR30/EGFR signaling pathway

doi:10.1016/j.ygyno.2013.02.005, Gynecologic Oncology 2013, 129, 433–442

Gynecologic Oncology

Objective The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Methods Cell proliferation was assayed by measuring the incorporation of 5′-bromo-2′-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14 days with K-1 (200 μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Results Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Conclusion Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling. Highlights ► K-1 inhibits endometrial cancer cellular growth and tumor xenograft growth via interfering with GPR30/EGFR/ERK1/2 activation. ► Compound showed dual targeting i.e. non-genomic GPR30 signaling and genomic ER signaling in endometrial cancer cells. ► Benzopyran derivative K-1 could serve as a candidate molecule for future development as a chemotherapeutic agent against human endometrial cancer.

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May 2013
1 Read

A highly efficient ultrasound-promoted synthesis of 2,3-disubstituted benzo[b]furans via intramolecular C-C bond formation in ionic liquid[bmim]BF4 at room temperature

RSC Adv., 2013,3, 540-544

RSC Advances

An efficient ultrasound-promoted synthesis of 2,3-disubstituted benzo[b]furans in the ionic liquid [bmim]BF4 at room temperature is reported. 5-exo-dig carbanion–yne intramolecular cyclization is mediated using anhydrous K3PO4 as a mild, inexpensive base under atmospheric conditions giving the title benzo[b]furans in excellent yields. Ionic liquid [bmim]BF4 has been used both as a reaction medium, as well as a catalyst for the C–C bond formation.

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July 2012
2 Reads

Apoptosis induction and inhibition of hyperplasia formation by 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran in rat uterus

American journal of obstetrics & gynaecology 362.e12-362.e11,2011

American journal of obstetrics & gynaecology

Objective The study was undertaken to explore the antiproliferative mechanism of action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) in estradiol-induced rat uterine hyperplasia. Study Design Adult ovariectomized rats received vehicle or estradiol alone (20 μg/kg) or estradiol along with K-1 (100 or 200 μg/kg) for 14 days. Uterine histomorphometric analysis and immunoblotting were performed. Caspase-3 activity and terminal deoxynucleotidyl transferase-mediated nick end-labeling staining were performed to analyze the apoptotic potential of compound. Results Compound inhibited estradiol-induced uterine weight and histomorphometric changes pertaining to endometrial growth and down-regulated the expression of estrogen response element and activator protein-1 regulated genes and transcription factors. The compound significantly induced apoptosis, interfered with Akt activation, decreased X-linked inhibitor of apoptosis protein expression leading to an increased cleavage of caspase-9, caspase-3, poly(adenosine diphosphate–ribose) polymerase, increased Bax/Bcl2 ratio, and caspase-3 activity. Conclusion K-1 inhibits endometrial proliferation via nonclassical estrogen receptor signaling mechanisms. It interfered with Akt activation and induced apoptosis via the intrinsic pathway and inhibited estradiol-induced hyperplasia formation in rat uterus.

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October 2011
1 Read

Eco-Friendly HClO4–SiO2 Catalyzed Synthesis of Mono- and Bis-diaryl-2H-1,4 Benzothiazines

Journal of Heterocyclic Chemistry, 2011, 1336

Journal of Heterocyclic Chemistry

Mono- and bis-diaryl-2H-1,4-benzothiazines were obtained in quantitative yields through silica-supported perchloric acid catalyzed reaction cascade of double condensation and 1,4 addition of diaroylacetylenes with 2-aminothiophenol at room temperature. The structures were confirmed by spectroscopic analyses and X-ray crystallographic studies. J. Heterocyclic Chem., (2011)

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August 2011
4 Reads

Benzopyran derivative CDRI-85/287 induces G2-M arrest in in estrogen receptor-positive breast cancer cells via modulation of estrogen receptor α and β signaling, in parallel to EGFR signaling and suppresses the growth of tumor xenograft

Steroid, 2013, 78, 1071

Steroid

In an endeavor to develop novel and improved selective estrogen receptor modulators as anti-breast cancer agents, the benzopyran compounds have been synthesized and identified which act as potent anti-estrogen at uterine level. The present study evaluates the anti-tumor activity of 2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzo(b)pyran (CDRI-85/287) and explores the mechanism of action with a view to describe its potential to inhibit proliferation in ER-positive breast cancer cells MCF-7 and T47D. The compound decreased the expression of ERα while increased the expression of ERβ thereby altering ERα/ERβ ratio in both cell lines. Although the compound showed low binding affinity to ERs, it acted as ERα antagonist and ERβ agonist in decreasing ERE- or AP-1-mediated transcriptional activation in these cells. Transactivation studies in ERα/β-transfected MDA-MB231 cells suggested that at cyclin D1 promoter, compound antagonized the action of ERα-mediated E2 response while acted as estrogen agonist via ERβ. Further, the compound led to decreased expression of ERα-dependent proliferation markers and ERβ-dependent cell cycle progression markers. The expression of cell cycle inhibitory protein p21 was increased leading to G2/M phase arrest. In parallel, compound also interfered with EGFR activation, caused inhibition of PI-3-K/Akt pathway and subsequent induction of apoptosis via intrinsic pathway. A significant reduction in tumor mass and volume was observed in 85/287-treated mice bearing MCF-7 xenograft. We conclude that compound 85/287 exhibits significant anti-tumor activity via modulation of genomic as well as non-genomic mechanisms involved in cellular growth and arrested the cells in G2 phase in both MCF-7 and T47D breast cancer cells. Study suggests that CDRI-85/287 may have therapeutic potential in ER-positive breast cancer.

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Top co-authors

Mohd Imran Ansari
Mohd Imran Ansari

CSIR-Central Drug Research Institute

3
Shahnaaz Khatoon
Shahnaaz Khatoon

D. N. (P.G.) College

2
Rituraj Konwar
Rituraj Konwar

CSIR-Central Drug Research Institute

1
Bandana Chakravarti
Bandana Chakravarti

CSIR-Central Drug Research Institute

1
Ruchir Kant
Ruchir Kant

CSIR-Central Drug Research Institute

1
Ashutosh Arun
Ashutosh Arun

CSIR-Central Drug Research Institute

1
Mohd M Khan
Mohd M Khan

King Saud University

1
Arun Kumar Rawat
Arun Kumar Rawat

CSIR-Central Drug Research Institute

1
Arvind Mishra
Arvind Mishra

Chhatrapati Sahuji Maharaj Medical University

1

Following

Shahnaaz Khatoon
Shahnaaz Khatoon

D. N. (P.G.) College