One Organic Chemist One Day............Honouring Profiles of leading Organic Chemists brought to you by DR ANTHONY MELVIN CRASTO, worlddrugtracker, helping millions, email@example.com, +91 9323115463, India, skype amcrasto64
DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 29Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution
Shashwati Basak obtained her PhD from Indian Institute of Science,
Bangalore, India. She carried out postdoctoral research from The Salk
Institute for Biological Sciences, San Diego and Stanford School of
Medicine, Palo Alto. Research in these two places was focused on
understanding the role of tumor suppressor p53 in Cancer Signaling
Pathways. She worked as a Research Scientist in the Veterans Affairs
Medical Center, San Francisco, before moving into the current role as a
Lead Investigator in Early Clinical and Translational Research, Biocon
Bristol-Myers Squibb Research and Development Center, Bangalore. Current
research interests involve assay development and qualification for
Clinical Biomarkers and its use in clinical sample analysis during drug
Biomarkers play a significant role during
all phases of drug discovery and development. Clinical biomarker-based
studies provide early information on target engagement, help guide
rational selection of drug combinations, optimization of dose and
schedule, serve as tools for stratifying patients and has the potential
to predict clinical outcome. A “fit-for purpose” assay development and
validation to meet the clinical requirements plays an important role in
biomarker estimation. While a rigorous validation is usually not
required for discovery-phase work, as a drug progresses into preclinical
and early-phase clinical evaluation, more thorough method validation
increasingly becomes valuable.
The real-time quantitative polymerase chain reaction (qPCR) technology
is accurate, sensitive and fast and has become the method of choice for
clinical biomarker detection and quantification. Numerous quality issues
may arise throughout the entire workflow influencing the accuracy of
the qPCR results and the reliability of the data interpretation and
conclusions. Development and use of qPCR technology for robust, accurate
and reliable method is required for the emerging “fit-for-purpose”
biomarker assay qualification. Key factors influencing assay performance
such as sample matrix, sample preparation, experimental precision,
reproducibility, sensitivity, specificity, dilution linearity and
dynamic range and their impact on the assay outcome will be discussed.
Based on these, we will put forth recommendations for consideration and
optimization while qualifying a qPCR-assay for analysis of clinical
samples. As biomarkers become integrated into drug development and
clinical trials, assay qualification becomes important with an
increasing emphasis on establishing standardized guidelines for
Research Professor; Director, Chemistry-Biochemistry-Biology Interface (CBBI) Program
Office: 247 NSH
Phone: (574) 631-2965
Dr. Chang obtained B.S. degrees in
biological sciences and chemistry from the University of Southern
California, and a Ph.D. in chemistry from the University of Chicago.
Subsequently, she conducted postdoctoral research at Columbia University
as a National Institutes of Health postdoctoral fellow. She joined the
faculty of the University of Notre Dame in 2003. Previously, Dr. Chang
was Chief Operating Officer of University Research Network,
Inc., Senior Scientist with Pharmacia Corporation, and Senior Chemist at
Dow Chemical Company. She has characterized the ADME properties
of numerous drugs, as well as prepared NDAs, INDs, Investigator’s
Brochures, product development plans, and candidate drug evaluations.
Research Professor; Director, Chemistry-Biochemistry-Biology Interface (CBBI) Program
The Chang lab conducts biomedical research to understand the
molecular basis of disease and to design small molecules for therapeutic
intervention. Some of our current projects are:
SB-3CT is a selective gelatinase (MMP-2 and MMP-9) inhibitor that
shows efficacy in animal models of stroke, traumatic brain injury, and
cancer metastasis. SB-3CT, however, is poorly water soluble and is
extensively metabolized. We used a prodrug strategy to increase
>5000-fold the aqueous solubility of SB-3CT. The prodrugs are
hydrolyzed in human blood within 30 minutes, generating the active
gelatinase inhibitors. One of the prodrugs (referred to as ND-478) has
excellent pharmacokinetic properties. This class of compounds is rapidly
absorbed andis readily distributed to the brain. Efficacy studies in
animal models of stroke and traumatic brain injury are currently being
Chronic wounds are a complication of diabetes and are characterized
by inflammation, altered MMP expression, and deregulation of apoptosis.
We used an affinity resin that binds only the active forms of MMPs and
related ADAMs coupled with quantitative proteomics to identify active
MMPs in diabetic wounds. Using the selective MMP-9 inhibitor ND-322 led
to acceleration of wound healing accompanied by re-epithelialization.
This represents the first pharmacological intervention in treatment of
diabetic wounds. Studies to confirm the roles of these MMPs in diabetic
wound healing are underway.
Another project involves the design, syntheses, and evaluation of novel antibiotics to treat methicillin-resistant Staphylococcus aureus infections.
We have identified two lead templates that show high in vitro activity
and promising antibacterial activity in a mouse model of infection.
Their pharmacokinetic properties are being optimized. Identification of
the target is being pursued by photoaffinity labeling at the whole
proteome level, as well as obtaining an X-ray crystal structure of the
compounds with the putative target.
Spink, E.; Ding, D.R.; Peng, Z.H.; Boudreau, M.A.; Leemans, E.;
Lastochkin, E.; Song, W.; Lichtenwalter, K.; O'Daniel, P.I.; Testero,
S.A.; Pi, H.L.; Schroeder, V.A.; Wolter, W.R.; Antunes, N.T.; Suckow,
M.A.; Vakulento, S.; Chang, M.; Mobashery, S. "Structure-Activity
Relationship for the Oxadiazole Class of Antibiotics." J. Med. Chem. 2015, 58 (3), 1380-1389.
Bouley, R.; Kumarasiri, M.; Peng, Z.H.; Otero, L.H.; Song, W.;
Suckow, M.A.; Schroeder, V.A.; Wolter, W.R.; Lastochkin, E.; Antunes,
N.T.; Pi, H.K.; Vakulento, S.; Hermoso, J.A.; Chang, M.; Mobashery, S.
"Discovery of Antibiotic
(E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one." J. Am. Chem. Soc. 2015, 137 (5), 1738-1741.
Ding, D.R.; Lichtenwalter, K.; Pi, H.L.; Mobashery, S.; Chang, M.
"Characterization of a selective inhibitor for matrix
metalloproteinase-8 (MMP-8)." MedChemComm 2014, 5 (9), 1381-1383.
O'Daniel, P.I.; Peng, Z.H.; Pi, H.L.; Testero, S.A.; Ding, D.R.;
Spink, E.; Leemans, E.; Boudreau, M.A.; Yamaguchi, T.; Schroeder, V.A.;
Wolter, W.R.; Llarrull, L.I.; Song, W.; Lastochkin, E.; Kumarasiri, M.;
Antunes, N.T.; Espahbodi, M.; Lichtenwalter, K.; Suckow, M.A.;
Vakulenko, S.; Mobashery, S.; Chang, M. "Discovery of a New Class of
Non-beta-lactam Inhibitors of Penicillin-Binding Proteins with
Gram-Positive Antibacterial Activity." J. Am. Chem. Soc. 2014, 136 (9), 3664-3672.
Gooyit, M.; Peng, Z.H.; Wolter, W.R.; Pi, H.L.; Ding, D.R.; Hesek,
D.; Lee, M.; Boggess, B.; Champion, M.M.; Suckow, M.A.; Mobashery, S.;
Chang, M. "A Chemical Biological Strategy to Facilitate Diabetic Wound
Healing." ACS Chem. Biol.2014, 9 (1), 105-110.
Gooyit, M.; Song, W.; Mahasenan, K.V.; Lichtenwalter, K.; Suckow,
M.A.; Schroeder, V.A.; Wolter, W.R.; Mobashery, S.; Chang, M. "O-Phenyl
Carbamate and Phenyl Urea Thiiranes as Selective Matrix
Metalloproteinase-2 Inhibitors that Cross the Blood Brain Barrier." J. Med. Chem. 2013, 56 (20), 8139-8150.
Research Professor, Chemistry & Biochemistry
University of Notre Dame Email: Mayland Chang
Office: 163 Stepan Hall
Mayland Chang, Department of Chemistry and Biochemistry, is working
on ways to inhibit cancer metastasis, the spreading of the
out-of-control cells to other organs. Although metastasis is a leading
reason that cancer becomes fatal, primary tumors rarely kill and often
can be treated, no anti-metastatic agent has been commercialized to
treat aggressive cancers. Meanwhile, metastasis of breast and prostate
cancer, for example, leads to further life-threatening complications
that cause tens of thousands of deaths each year.
Building on studies showing that the matrix metal-loproteinases are
associated with cancer progression and metastasis in many types of
cancers, a few years ago discovered and
synthesized the first prototype selective mechanism-based inhibitor
found to be effective in mouse models of prostate cancer metastasis to
the bone, breast cancer metastasis to the lungs, and T-cell lymphoma
metastasis to the liver. This work has progressed in the direction of
compounds that can be used in additional in vivo models for disease,
leading to second and third-generation compounds. The researchers are
now refining related compounds with the goal of developing selective
inhibitors that can advance forward to preclinical development and
ultimate entry into clinical trials for the treatment of cancer
Five Questions with Mayland Chang
Chang, PhD, is bringing scientific discoveries out of academia to the
masses, from new antibiotics to the treatment of skull-crunching head
injuries on the football field.
Chang, a faculty member in
the Department of Chemistry and Biochemistry, was recently awarded a
five year, $5.5 million dollar grant from the National Institute of
Allergy and Infectious Diseases (NIAID). She is also the recent
recipient of an NFL Charities grant to design and develop therapeutics
for the treatment of traumatic brain injury (TBI).
NIAID grant, a considerably large amount for research grants, will fund
translational research aimed at the discovery and development of drugs
to fight serious gram-positive bacterial infections such as
methicillian resistant Staphylococcus aureus (MRSA). Translational
research is described by Chang as “bench to bedside” research, which
leads to practical applications in patients.
B.S. degrees in biological sciences and chemistry from the University
of Southern California, and a Ph.D. in chemistry from the University of
Chicago. She joined Notre Dame in 2003.
Chang recently spoke with ND Today about her research, teaching at Notre Dame, and her hobbies.
ND Today: What does it mean to you to receive the NIAID grant?
There is a dearth of research on new antibacterials, as the economic
incentives are not there for pharmaceutical companies to pursue
discovery and development of antibiotics. Because fewer pharmaceutical
companies are focusing on antibacterials (most have abandoned the
field), academic institutions have to step up to discover and develop
new classes of antibiotics. This grant allows us to do just that.
ND Today: Tell us about your NFL Charities Grant – what type of research will you be doing?
Traumatic brain injury (TBI) is one of the leading causes of death and
disability in the industrialized world. A TBI is caused by a bump,
blow, or jolt to the head or a penetrating head injury that disrupts
the normal function of the brain. The majority of TBIs (75%) are
concussions. Concussions are a prominent feature of sports, with
300,000 reported concussions in the U.S. occurring while playing
sports. Concussions result from a blow to the head that produces a
cascade of neurological events, resulting in reduced blood flow to the
brain, brain cell injury, and death.
A contributing factor
to these pathological processes is the activation of enzymes called
matrix metalloproteinases (MMPs), particularly gelatinases (MMP-2 and
MMP-9). There are presently no therapeutics for TBI. Research in the
field lacks presently the ability to rescue brain cells after each
concussion or any damage to the brain. If a medication could be given
after such a damage that rescues the brain cells destined to die that
would move the field forward in treatment of TBI significantly. The NFL
Charities grant will support groundbreaking research that has the
potential for the development of such a treatment for TBI. We have
developed a prototype inhibitor, which potently decreases brain damage
and hemorrhagic injury. We have synthesized water-soluble inhibitors,
which are amenable to intravenous administration, the preferred route
of administration for TBI. These results hold outstanding promise for
important applications in fighting gelatinase-mediated consequences of
brain damage after TBI in patients.NFL funding will open the door for
expansion of this project in directions that we hope will lead to
treatments for TBI.
ND Today: How did you come to specialize in chemistry?
I grew up in Ecuador and was good in math and science. As a high school
student, I only knew of professional careers, such as medicine. I came
to the US for college and as an undergraduate at USC I started as a
biology major. There was no pre-med major at USC. After taking
analytical chemistry as a junior in college, I decided to pursue
chemistry. I ended up with a BS in biology and a BS in chemistry. Then I
went to graduate school at the University of Chicago and got my PhD as
a natural products chemist and post-doc at Columbia University in
bioanalytical chemistry. When I was looking for a job, I could not find
a position in the industry in natural products chemistry. I ended up
doing metabolism of herbicides and insecticides at Dow Chemical. From
there I moved to Upjohn. Before moving to Notre Dame, I was COO of
University Research Network, Inc., an academic research organization
that I established for Wayne State University School of Medicine that
facilitated clinical research and provided clinical development
services to the pharmaceutical and biotechnology industries.
ND Today: What is the best part about working at Notre Dame?
The opportunity to work with and train talented undergraduate students.
Since I came to Notre Dame, I have had nine undergraduates in the
lab—four have graduated, one is in grad school at Madison Wisconsin,
one is in an MD PhD program at Washington University, one is in an MD
program at Loyola, and one is in an MD program at Rochester.
ND Today: Given the very serious nature of your work, what do you like to do to unwind?
Gourmet cooking. Cooking is very much like chemistry. I wanted to be a
chef but it was not an acceptable profession [in her home country].
Gardening—pulling weeds relieves stress, and travel—traveling is part
of one’s education—it opens the mind to new experiences and cultures. I
love to spend time with my cats Misty and Carbon, and watching birds
in my backyard. Rain or shine, I feed the birds year-round.
Mayland Chang receives $1.6M American Diabetes Association research award
Diabetes affects more than 29 million Americans, or 9.3 percent of
the population. One of the many complications of the disease is the
inability of wounds to heal properly because diabetic patients often
have nerve damage, weakened immune systems or narrow arteries. In 2010,
73,000 non-traumatic lower-limb amputations were performed in the United
States due to diabetes.
The American Diabetes Association (ADA) announced Tuesday that it is funding a $1.6 million Accelerator Award to Mayland Chang,
research professor of chemistry and biochemistry at the University of
Notre Dame, to help lower that number. The research award, part of the
association’s Pathway Awards program, will provide funding for Chang’s
project, “A Strategy to Accelerate Diabetic Wound Repair,” over five
Chang’s research is broadly focused on exploring the molecular basis
of disease and designing small molecules for therapeutic interventions.
She has ongoing projects related to stroke, traumatic brain injury,
cancer metastasis and MRSA
(methicillin-resistant Staphylococcus aureus). A newer area of work for
Chang is to understand why diabetic wounds are so difficult to treat and
to develop novel therapeutics to promote wound healing.
Using a mouse model and a novel diagnostic resin that binds to active
forms of matrix metalloproteinases (MMPs), proteases involved in tissue
remodeling, Chang’s research group found that MMP-9 may cause diabetic wounds and MMP-8 may be involved in wound repair. They also demonstrated that selective pharmacological inhibition of MMP-8 delayed wound repair and inhibition of MMP-9 accelerated wound healing.
Using a combination of research techniques, Chang’s project will
identify the mechanisms associated with diabetic wound development,
progression and healing; study bacterial colonization in diabetic
wounds; and find interventions that expedite the healing process. To
achieve these goals, she will validate the roles of MMP-8 and MMP-9 in diabetic wounds, investigate the relevance of these MMPs in human patients, evaluate novel MMP-9 inhibitors and determine the contribution of bacterial infection on wound repair.
“This research project will allow intervention of chronic wounds, a
complication of diabetes for which pharmacological clinical recourse is
not available,” Chang said. “Our work holds great promise in addressing
an unmet medical need.”
Accelerator Awards are designed to support early-career investigators
or established researchers who are accomplished in other fields, but
would like to apply their expertise to innovative diabetes-related
research topics. Contact: Mayland Chang, 574-631-2965, firstname.lastname@example.org
am an interdisciplinary PhD candidate that headed an antibiotic
discovery project resulting in a patent application and 1 first-author
publication in Journal of the American Chemical Society. I have been
trained in organic chemistry, microbiology, biochemistry, pharmacology,
and x-ray crystallography and co-authored 4 publications including 1
publication in Nature Chemical Biology. Additionally, I have been
awarded 2 individual fellowships during my graduate career from the
American Chemical Society and National Institutes of Health.
Synthesized 40 analogs and determined a structure-activity relationship.
Determined metabolic stability and plasma stability of synthetic compounds
Evaluated synthetic compounds in mouse models of infection
Identified the biological target and mechanism of action of synthetic
compounds by protein activity assays, protein-ligand crystal complexes,
and macromolecular synthesis assays
Grew crystals of membrane protein and performed co-crystallization studies with ligands
Measured protein crystals at the Swiss Light Source in Zurich, Switzerland
Analyzed the diffraction data by molecular replacement
Supervised and instructed students majoring in chemistry in organic chemistry techniques
Graded weekly lab reports and course exams
Spring 2011 & Fall 2011:
Led weekly discussion sections in which students worked on problem sets
Gave short lectures on the background information needed to complete each problem set
Graded weekly problem sets and course exams
Synthesized a polyaniline matrix and incorporated onto electrodes
Measured polyaniline matrices by electrochemical impedance spectroscopy (EIS)
Measured resistance and capacitance of a redox protein, cytochrome c, by EIS
Evaluated anti-inflammatory activity of botanical extracts using a MMP-9 protein activity assay
Evaluated botanical extracts for effects on melanonin production using a mouse tryosinase protein activity assay
Quantified solubility of active ingredients in botanical extracts using HPLC
Honors & Awards
Baxter Young Investigator Award
Second Tier Awardee for Baxter Young Investigator Award
Staphylococcus aureus (MRSA) is one of the most prevalent
multidrug-resistant pathogens worldwide, exhibiting increasing
resistance to the latest antibiotic therapies. Here we show that the
triple β-lactam combination meropenem-piperacillin-tazobactam (ME/PI/TZ)
acts synergistically and is bactericidal against MRSA subspecies N315
and 72 other clinical MRSA isolates in vitro...more
Renee Bouley selected to receive prestigious ACS Predoctoral Fellowship
Published: July 02, 2013
Renee Bouley, a third year graduate student in the Department of Chemistry and Biochemistry,
has been selected to receive a prestigious American Chemical Society
(ACS) Division of Medicinal Chemistry Predoctoral Fellowship. Bouley is
one of only four recipients chosen for the 2013-2014 cycle.
This award supports doctoral candidates working in the area of
medicinal chemistry who have demonstrated superior achievements as
graduate students and who show potential for future work as independent
investigators. These fellowships have been awarded annually since 1991
and include one year stipend support and an invitation to present the
fellow’s research results at a special awards session at the ACS
Bouley’s work, conducted under the advisement of Shahriar Mobashery, Navari Family Professor in Life Sciences, and Mayland Chang,
Research Professor and Director of the Chemistry-Biochemistry-Biology
Interface (CBBI) Program, centers around the discovery of a new class of
antibiotics that are selective against staphylococcal species of
bacteria, including hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA). She has already identified a class of compounds that has in vitro
activity against bacteria and demonstrated efficacy in mice. Bouley
spent three months in 2012 in the laboratory of Prof. Juan Hermoso at
Consejo Superior de Investigaciones Cientificas in Madrid, Spain, where
she solved the crystal structure of the lead compound in complex with
its target protein. Her studies have shown an unprecedented mechanism of
action that opens opportunities for clinical resurrection of β-lactam
antibiotics in combination with the new antibiotics. Bouley’s work
during her fellowship tenure will explore structural analogs of these
compounds with the goal of optimizing their potency in vivo and improving their drug-like properties.
Bouley is already the recipient of a National Institutes of Health
Ruth L. Kirschstein National Research Service Award – CBBI
(Chemistry-Biochemistry-Biology Interface) Program, a CBBI Research
Internship Award, and an American Heart Association Predoctoral
Aug 2010– present
University of Notre Dame · Department of Chemistry and Biochemistry · Shahriar Mobashery
United States · South Bend
May 2009– Aug 2009
Amway · Analytical Services
Jan 2008– May 2010
Grand Valley State University · Department of Chemistry
Aug 2010– Dec 2015
University of Notre Dame
Chemistry · PhD
Aug 2006– May 2010
Grand Valley State University
Chemistry · BS
USA · Grand Rapids
Awards & achievements
Award: Ruth L. Kirschstein NRSA Individual Predoctoral Fellowship
• Synthesis of New Chemical entities particularly antibiotics, β-lactam inhibitor molecules based upon SAR.
• Proposing and designing synthetic route for newer molecule and its synthesis with more than 90% HPLC.
• One of the major work includes synthesis and method development of WCK 5178 one of the lead molecule. During the development of this molecules developed coupling of Na-DBO core with hydrazide in water, which is the key step in the synthesis. Synthesis of all known impurities of WCK 5178.
• Synthesis and scale up of DBO core, one of the most important key intermediate for WCK 5178 by patentable route
• Identification of unknown and major impurity based upon NMR, formed during the synthesis of side chain of WCK 5178 at plant scale.
• Proposed and attempted synthesis of side chain of another promising lead molecule WCK 5153.
Worked on “Some Studies on [3+2] Cycloadducts” which includes:
• 1,3-Dipolar reactions of nitrile oxide with alkene and alkynes, click chemistry of azides and alkynes.
• The studies includes synthesis of few known and unknown 1,3-dipoles particularly nitrile oxides and azides.
• Employed these dipoles and dipolarophiles in cycloaddition study and to establish regio- and stereochemistry of the newly formed cycloadducts by spectral and chemical correlation.
• Applications of 1,3-dipolar cycloaddition reactions as a tool for the synthesis of bioconjugates particularly steroid and carbohydrate based conjugates.