PMID- 38060834
OWN - NLM
STAT- Publisher
LR  - 20231207
IS  - 2191-1363 (Electronic)
IS  - 2191-1363 (Linking)
DP  - 2023 Dec 7
TI  - Identifying Phosphodiesterase-5 Inhibitors with Drug Repurposing Approach: 
      Implications in Vasodysfunctional Disorders.
PG  - e202300196
LID - 10.1002/open.202300196 [doi]
AB  - Phosphodiesterase type 5 (PDE5) is a multidomain protein that plays a crucial 
      role in regulating cellular cyclic guanosine monophosphate (cGMP), a key 
      signaling molecule involved in various physiological processes. Dysregulation of 
      PDE5 and cGMP signaling is associated with a range of vasodysfunctional 
      disorders, necessitating the development of effective therapeutic interventions. 
      This study adopts comprehensive approach, combining virtual screening and 
      molecular dynamics (MD) simulations, to repurpose FDA-approved drugs as potential 
      PDE5 inhibitors. The initial focus involves selecting compounds based on their 
      binding affinity. Shortlisted compounds undergo a meticulous analysis for their 
      drug profiling and biological significance, followed by the activity evaluation 
      and interaction analysis. Notably, based on binding potential and drug profiling, 
      two molecules, Dutasteride and Spironolactone, demonstrate strong potential as 
      PDE5 inhibitors. Furthermore, all atom MD simulations were employed (500 ns) to 
      explore dynamic behavior of Dutasteride and Spironolactone in complexes with 
      PDE5. Principal components analysis (PCA) and free energy landscape (FEL) 
      analyses are further leveraged to decipher that the binding of Dutasteride and 
      Spironolactone stabilizes the structure of PDE5 with minimal conformational 
      changes. In summary, Dutasteride and Spironolactone exhibit remarkable affinity 
      for PDE5 and possess characteristics that suggest their potential as therapeutic 
      agents for conditions associated with PDE5 dysfunction.
CI  - (c) 2023 The Authors. ChemistryOpen published by Wiley-VCH GmbH.
FAU - Khan, Mohd Shahnawaz
AU  - Khan MS
AD  - Department of Biochemistry, College of Science, King Saud University, KSA.
FAU - Mohammad, Hamza Ahmad
AU  - Mohammad HA
AD  - Department of Biochemistry, College of Science, King Saud University, KSA.
FAU - Shahwan, Moyad
AU  - Shahwan M
AD  - Center for Medical and Bio-Allied Health Sciences Research, Ajman University 
      (UAE).
FAU - Yadav, Dharmendra Kumar
AU  - Yadav DK
AD  - Gachon Institute of Pharmaceutical Science and Department of Pharmacy, College of 
      Pharmacy, Gachon University, Incheon (Republic of, Korea.
FAU - Anwar, Saleha
AU  - Anwar S
AD  - Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, 
      Jamia Nagar, New Delhi, 110025, India.
FAU - Shamsi, Anas
AU  - Shamsi A
AUID- ORCID: 0000-0001-7055-7056
AD  - Center for Medical and Bio-Allied Health Sciences Research, Ajman University 
      (UAE).
LA  - eng
GR  - RSP2023R352/King Saud University/
GR  - Ajman University/
PT  - Journal Article
DEP - 20231207
PL  - Germany
TA  - ChemistryOpen
JT  - ChemistryOpen
JID - 101594811
SB  - IM
OTO - NOTNLM
OT  - drug design
OT  - drug repurposing
OT  - molecular dynamics
OT  - signaling molecules
OT  - virtual screening
EDAT- 2023/12/07 18:42
MHDA- 2023/12/07 18:42
CRDT- 2023/12/07 15:58
PHST- 2023/10/12 00:00 [revised]
PHST- 2023/09/20 00:00 [received]
PHST- 2023/12/07 18:42 [medline]
PHST- 2023/12/07 18:42 [pubmed]
PHST- 2023/12/07 15:58 [entrez]
AID - 10.1002/open.202300196 [doi]
PST - aheadofprint
SO  - ChemistryOpen. 2023 Dec 7:e202300196. doi: 10.1002/open.202300196.