Hiba Najeh Al-Saad, Ammar A. Razzak Mahmood Kubba
Hiba Najeh Al-Saad1, Ammar A. Razzak Mahmood Kubba2*
1Department of Pharmaceutical Chemistry, College of Pharmacy, Basrah University, Basrah- Iraq.
2Department of Pharmaceutical Chemistry, College of Pharmacy- University of Baghdad, Baghdad, 10001-Iraq.
Volume - 13,
Issue - 6,
Year - 2020
A series of new captopril thiosemicarbazide derivatives (2-7) were evaluated in vitro for ACE inhibitor activity, using developed colorimetric assay as a simple, sensitive, and cost-effective method. Compounds (4 and 7), substituted with an electron-withdrawing group, showed good ACE inhibition activity, compared to non-substituted derivatives, and compounds substituted with electron-donating groups, with percent inhibition of 76.23±0.44 and 79.22±0.25, and IC50 (0.137 and 0.103 µ?), respectively. The molecular docking study revealed good agreement for compounds (4 and 7) with in vitro findings, respectively, with binding energy (-6.99 and -7.3 Kcal / mol). In silico pre-ADMET analysis, all derivatives are supposed to show appropriate intestinal absorption with low BBB penetration, and a closer carcinogenicity score to zero. The lipophilicity of the synthetic compounds, expressed with Clog p values, showed good correlation with in vitro ACE inhibition activity.
Cite this article:
Hiba Najeh Al-Saad, Ammar A. Razzak Mahmood Kubba. Evaluation of New Thiosemcarbazides Derived from Captopril as Angiotensin-Converting Enzyme Inhibitors with Docking Study, and Predicted-ADMET Analysis. Research J. Pharm. and Tech 2020; 13(6): 2733-2741. doi: 10.5958/0974-360X.2020.00486.2
1. Bonesi M, Loizzo MR, Statti GA, Michel S, Tillequin F, Menichini F. The synthesis and angiotensin converting enzyme (ACE) inhibitory activity of chalcones and their pyrazole derivatives. Bioorganic and Medicinal Chemistry Letters. 2010;20(6):1990-1993.
2. Kwon M-J, Ahn S-Y. Factors affecting blood pressure control in elderly Koreans with hypertension. Research Journal of Pharmacy and Technology. 2018;11(4):1398-1403.
3. Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. Journal of managed care pharmacy. 2007;13(8 Supp B):9-20.
4. Muñoz-Durango N, Fuentes CA, Castillo AE, González-Gómez LM, Vecchiola A, Fardella CE. Role of the renin-angiotensin-aldosterone system beyond blood pressure regulation: molecular and cellular mechanisms involved in end-organ damage during arterial hypertension. International journal of molecular sciences. 2016;17(7):2-17.
5. Rekha R, Anju G, Shishant S, Sheefali M, Sanju N. Effect of chemical enhancers on in-vitro permeation of Losartan potassium. Research Journal of Pharmacy and Technology. 2012;5(3): 346-352.
6. Persson PB. Renin: origin, secretion and synthesis. The Journal of Physiology. 2003;552(Pt 3):667-71.
7. Kurtz A. Control of Renin Synthesis and secretion. American Journal of Hypertension. 2012;25(8):839-847.
8. van Sande ME, Scharpé SL, Neels HM, Van Camp KO. Distribution of angiotensin converting enzyme in human tissues. Clinica Chimica Acta. 1985;147(3):255-260.
9. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney International. 2005;68:S57-S65.
10. Kumar KA, Jagannath P, Saleshier MF. Discovery of novel flavonoid analogues as angiotensin converting enzyme inhibitors based on pharmacophore modelling and virtual screening techniques. Research Journal of Pharmacy and Technology. 2018;11(10):4370-4378.
11. Coates D. The angiotensin converting enzyme (ACE). The international journal of biochemistry and cell biology. 2003;35(6):769-73.
12. Zhao Y, Xu C. Structure and function of angiotensin converting enzyme and its inhibitors. Chinese Journal of Biotechnology. 2008;24(2):171-176.
13. Duchin KL, McKinstry DN, Cohen AI, Migdalof BH. Pharmacokinetics of captopril in healthy subjects and in patients with cardiovascular diseases. Clinical pharmacokinetics. 1988;14(4):241-259.
14. Bahadur S, Chanda R, Roy A, Choudhury A, Das S, Saha S. Preparation and evaluation of mucoadhesive microcapsules of captopril for oral controlled release. Research Journal of Pharmacy and Technology. 2008;1(2):100-105.
15. Lee PW. Handbook of Metabolic Pathways of Xenobiotics: John Wiley and Sons Incorporated; 2014.
16. Migdalof BH, Antonaccio MJ, McKinstry DN, Singhvi SM, Lan SJ, Egli P. Captopril: pharmacology, metabolism and disposition. Drug metabolism reviews. 1984;15(4):841-869.
17. Jaiswal H, Ansari VA, Pandit J, Ahsan F. Pulsatile Drug delivery system: An overview with special emphasis on Losartan and Captopril. Research Journal of Pharmacy and Technology. 2019;12(7):3175-3188.
18. Bevilacqua M, Vago T, Rogolino A, Conci F, Santoli E, Norbiato G. Affinity of angiotensin I-converting enzyme (ACE) inhibitors for N- and C-binding sites of human ACE is different in heart, lung, arteries, and veins. Journal of cardiovascular pharmacology. 1996;28(4):494-499.
19. Attoub S, Gaben AM, Al‐Salam S, Al Sultan M, John A, Nicholls MG. Captopril as a potential inhibitor of lung tumor growth and metastasis. Annals of the New York Academy of Sciences. 2008;1138(1):65-72.
20. Bartosz M, Kedziora J, Bartosz G. Antioxidant and prooxidant properties of captopril and enalapril. Free Radical Biology and Medicine. 1997;23(5):729-735.
21. Skowasch D, Viktor A, Schneider-Schmitt M, Lüderitz B, Nickenig G, Bauriedel G. Differential antiplatelet effects of angiotensin converting enzyme inhibitors. Clinical research in cardiology. 2006;95(4):212-216.
22. Atkinson A, Robertson J. Captopril in the treatment of clinical hypertension and cardiac failure. The Lancet. 1979;314(8147):836-839.
23. Hiba NAS, Ammar A.Razzak Mamood , Redha I.AB. Design, synthesis, docking study and antiplatelet evaluation of new thiosemicarbazide derivatives derived from captopril. Oriental journal of chemistry. 2019;35(2): 829-838.
24. Costa MFdM, Carmona AK, Alves MF, Ryan TM, Davies HM, Anderson GA. Determination of angiotensin I-converting enzyme activity in equine blood: lack of agreement between methods of analysis. Journal of veterinary science. 2011;12(1):21-25.
25. Islamudin Ahmad AY, Kamarza M, Abdul Mun'im. Review of angiotensin-converting enzyme inhibitory assay: Rapid method in drug discovery of herbal plants. pharmacognasy review. 2017;11(21):1-7.
26. Patil PR, Rakesh SU, Dhabale PN, Burade KB. Simultaneous estimation of ramipril and amlodipine by UV spectrophotometric method. Research Journal of Pharmacy and Technology. 2009;2(2):304-307.
27. Zhuang X-d, Liao L-z, Dong X-b, Hu X, Guo Y, Du Z-m. Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ace inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases. Drug design, development and therapy. 2016;10:129-140.
28. Jimsheena V, Gowda LR. Colorimetric, high-throughput assay for screening angiotensin I-converting enzyme inhibitors. Analytical chemistry. 2009;81(22):9388-9394.
29. Chen J, Wang Y, Ye R, Wu Y, Xia W. Comparison of analytical methods to assay inhibitors of angiotensin I-converting enzyme. Food chemistry. 2013;141(4):3329-3334.
30. Sharifi N, Souri E, Ziai SA, Amin G, Amanlou M. Discovery of new angiotensin converting enzyme (ACE) inhibitors from medicinal plants to treat hypertension using an in vitro assay. DARU Journal of Pharmaceutical Sciences. 2013;21(1):1-8.
31. Wu S, Sun J, Tong Z, Lan X, Shu B, Liu Y, et al. Rapid and simple colorimetric assay for screening angiotensin I-converting enzyme inhibitors. Pharmaceutical biology. 2012;50(10):1303-1309.
32. Masuyer G, Douglas RG, Sturrock ED, Acharya KR. Structural basis of Ac-SDKP hydrolysis by angiotensin-I converting enzyme. Scientific reports. 2015;5:1-12.
33. Eissa IH, El-Naggar AM, El-Sattar NE, Youssef AS. Design and discovery of novel quinoxaline derivatives as dual DNA intercalators and topoisomerase II inhibitors. Bentham science. 2018;18(2):195-209.
34. Hardjono S, Widiandani T, Purwanto BT, Nasyanka AL. Molecular docking of N-benzoyl-N’-(4-fluorophenyl) thiourea derivatives as anticancer drug candidate and their ADMET prediction. Research Journal of Pharmacy and Technology. 2019;12(5):2160-2166.
35. Rudraraju A, Amoyaw P, Hubin T, Khan M. Determination of log p values of new cyclen based antimalarial drug leads using RP-HPLC. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2014;69(9):655-662.
36. Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. Journal of medicinal chemistry. 2002;45(12):2615-2623.