PMID- 35909284
OWN - NLM
STAT- MEDLINE
DCOM- 20221114
LR  - 20221215
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 28
IP  - 36
DP  - 2022
TI  - Inhibitory Efficacy of Thiosemicarbazones for Carbonic Anhydrase II (Bovine and 
      Human) as a Target of Calcification and Tumorigenicity.
PG  - 3010-3022
LID - 10.2174/1381612828666220729105849 [doi]
AB  - BACKGROUND: Carbonic anhydrase II (CA-II) is associated with calcification, 
      tumorigenicity, epilepsy, osteoporosis, and several other physiological or 
      pathological processes. CA-II inhibitors can be used to reduce the intraocular 
      pressure usually associated with glaucoma. OBJECTIVE: In search for potent CA-II 
      inhibitors, a series of thiosemicarbazone derivatives (3a-u) was synthesized. 
      METHODS: This series was evaluated against bovine and human carbonic anhydrase II 
      (bCA-II and hCA-II) and their docking studies were carried out. RESULTS: In the 
      preliminary screening, most of the compounds exhibited significant inhibition of 
      bCA-II and hCA-II. The predictive structure-activity relationship suggested that 
      the thiosemicarbazide moiety plays a key role in the inhibition of enzyme 
      activity and substitution at R position and has a remarkable contribution to the 
      overall activity. The kinetic studies of the most active inhibitors of bCA-II 
      (3d, 3e, 3l, 3f, and 3p) and hCA-II (3g) were performed against bCA-II and 
      hCA-II, respectively to investigate their mode of inhibition and dissociation 
      constants (Ki). CONCLUSION: Subsequently, (3e, 3f, 3l and 3p) were identified as 
      competitive inhibitors of bCA-II with Ki values of 5.02-14.70 muM, while (3d) as a 
      noncompetitive inhibitor of bCA-II (Ki = 2.5 +/- 0.015 muM), however, (3g) 
      demonstrated competitive inhibition of hCA-II with a Ki value of 5.95 +/- 0.002 muM. 
      The selectivity index reflects that compound (3g) is more selective for hCA-II. 
      The binding modes of these compounds with bCA-II and hCA-II were investigated by 
      structure-based molecular docking, and the docking results are in complete 
      agreement with the experimental findings.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Khan, Majid
AU  - Khan M
AD  - Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 
      Birkat Al Mauz, Nizwa, Oman.
AD  - International Center for Chemical and Biological Sciences, H.E.J. Research 
      Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan.
FAU - Halim, Sobia Ahsan
AU  - Halim SA
AD  - Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 
      Birkat Al Mauz, Nizwa, Oman.
FAU - Shafiq, Zahid
AU  - Shafiq Z
AD  - Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, 
      Pakistan.
FAU - Islam, Muhammad
AU  - Islam M
AD  - Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, 
      Pakistan.
FAU - Shehzad, Muhammad Tariq
AU  - Shehzad MT
AD  - Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, 
      Pakistan.
FAU - Ibrar, Aliya
AU  - Ibrar A
AD  - Department of Chemistry, Faculty of Natural Sciences, The University of Haripur, 
      Haripur, KPK-22620, Pakistan.
FAU - Khan, Farhan A
AU  - Khan FA
AD  - Department of Chemistry, COMSATS University Islamabad Abbottabad Campus, 
      Abbottabad, Pakistan.
FAU - Marraiki, Najat
AU  - Marraiki N
AD  - Department of Botany and Microbiology, College of Science, King Saud University, 
      Riyadh 11451, Saudi Arabia.
FAU - Uddin, Jalal
AU  - Uddin J
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid 
      University, Abha 62529, Saudi Arabia.
FAU - Khan, Ajmal
AU  - Khan A
AD  - Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 
      Birkat Al Mauz, Nizwa, Oman.
FAU - Al-Harrasi, Ahmed
AU  - Al-Harrasi A
AD  - Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 
      Birkat Al Mauz, Nizwa, Oman.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - 0 (Thiosemicarbazones)
RN  - 0 (Carbonic Anhydrase Inhibitors)
SB  - IM
MH  - Humans
MH  - Cattle
MH  - Animals
MH  - *Carbonic Anhydrase II/metabolism
MH  - *Thiosemicarbazones/pharmacology
MH  - Molecular Docking Simulation
MH  - Kinetics
MH  - Carbonic Anhydrase Inhibitors/pharmacology/chemistry
MH  - Structure-Activity Relationship
MH  - Molecular Structure
OTO - NOTNLM
OT  - Thiosemicarbazone
OT  - bovine
OT  - carbonic anhydrase II
OT  - human
OT  - kinetics studies
OT  - molecular docking
EDAT- 2022/08/02 06:00
MHDA- 2022/11/15 06:00
CRDT- 2022/08/01 01:23
PHST- 2022/04/06 00:00 [received]
PHST- 2022/06/27 00:00 [accepted]
PHST- 2022/08/02 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/08/01 01:23 [entrez]
AID - CPD-EPUB-125227 [pii]
AID - 10.2174/1381612828666220729105849 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2022;28(36):3010-3022. doi: 10.2174/1381612828666220729105849.