| dc.description |
On the accomplishment of the present study, I would like to take this opportunity to extend my
deepest sense of gratitude and words of appreciation towards those, who helped me during the
pursuit of study. I deem it a proud privilege and feel immense pleasure to acknowledge all those
who are directly or indirectly involved. I am thankful to the most Gracious, Merciful and
Almighty Allah who gave me the health, thoughts and opportunity to complete this work.
Words are inadequate in the available lexicon to avouch the excellent guidance given by my
supervisor Major Mohammad Neaz Morshed, PhD, Associate Professor, Department of
Chemistry, Military Institute of Science and Technology (MIST). His words of encouragement,
endless inspiration, extensive support, scholastic guidance, inertness patience, and excellent
counsel helped me to complete the research and thesis paper as accurately as possible. His
dedication to research, meticulous planning, consecutive counsel, and unreserved help served as
a beacon light throughout the course of study, and completion of this manuscript and guiding
through my whole research work.
I would like to express my heartfelt gratitude to Mohammad A. Halim, PhD, CEO of The Red-
Green Research Centre, for his dedication to research, words of encouragement, kind advice,
mental support and for allowing me the lab facilities The Red-Green Research Centre.
I am also thankful to Major Palash Kumar Sarker, PhD, Associate Professor, Department of
Chemistry, MIST for his deep inspiration, teaching, guidance and meticulous research insight
that made me a success to complete this research work.
I convey my sincere gratitude to Cdr M Ziaul Ahsan, BN, Professor and Head, Science and
Hum Department, MIST for his kind cooperation and support to during my M. Phil study and
research. |
en_US |
| dc.description.abstract |
Apoptosis, a process of programmed cell death controlled by a defined apoptotic pathway, plays
an important role in the development of all multicellular organisms. Any alterations in apoptotic
pathways have been implicated in Cancer, one of the most deadly diseases in the world and
Bangladesh as well. The pathway of Apoptosis is executed with a cascade of sequential
activation of initiator and effector caspases, a family of proteases found in Apoptotic pathways to
induce Apoptosis during abnormal cell growth in the cell cycle. Due to limited number of
successful inhibitors in the market as well as pharmacological constraints of designed and tested
peptide and peptidomimetic inhibitors against Caspase protein, In this study, In Silico approach
like Virtual Screening with Molecular Docking applied to identify potential lead compounds
against Pro-Caspase 7, one of the effector proteins of Apoptotic signaling proteins and 1571
drug-like molecules downloaded from the Binding database and ZINC database and identified
four potential lead compounds. Noncovalent interactions like hydrogen bond, halogen bond,
hydrophobic interaction, electrostatic interaction are examined among all the identified potential
lead compounds and Pro-Caspase 7 after Molecular Docking study. In addition, Molecular
dynamics study conducted to test the feasibility of the identified compounds in biological
systems and again checked Molecular Docking energy and binding interactions for the Pro-
Caspase 7 protein. Molecular dynamics study significantly increased binding energies among
Pro-Caspase 7 and the first and third potential lead compounds and that are -15.8 and -14.3
kcalmol−1 respectively. Pharmacoinformatics analysis predicts that all potential lead compounds
are non-carcinogenic and nonmutagenic. And, hence considering Molecular Docking study,
Molecular dynamics study and Pharmacoinformatics study, the identified four potential lead
compounds can induce Pro-Caspase 7 to Caspase which leads to Apoptosis and ultimately works
for Cancer treatment.
Although this in silico study helps the researchers and pave the way for Anti-Cancer drug
development, further wet lab assessment of these potential lead compounds has to be performed. |
en_US |
