Limits...
Molecular docking study and antiviral evaluation of 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives.

Al-Salahi R, Abuelizz HA, Ghabbour HA, El-Dib R, Marzouk M - Chem Cent J (2016)

Bottom Line: The cytotoxicity (CC50), effective concentration (EC50) and the selectivity index (SI) values were determined.Based on their EC50 values, a number of the investigated compounds demonstrated weak to moderate activity relative to their parents.Accordingly, compounds 5-9, 11, 15-18, 21, 22, 24, 25, 27 and 28 were active against CVB4, and compounds 5 and 24 were active against HSV-1 and 2 in comparison to ribavirin and acyclovir, which were used as reference drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451 Saudi Arabia.

ABSTRACT

Background: The persistent appearance of viral strains that causes a resistant viral infection has led to continuous trials for the design and development of novel antiviral compounds. Benzoquinazoline compounds have been reported to exhibit an interesting antiviral activity. This work aims to study and evaluate the antiviral activity of a newly prepared 2-thioxo-benzo[g]quinazolin-4(3H)-one series against herpes simplex (HSV-1 & 2) and coxsackievirus (CVB4).

Methods: The antiviral activity was performed using the MTT assay, in which Vero cells (obtained from the American Type Culture Collection, ATCC) were propagated in fresh Dulbecco's Modified Eagle's Medium (DMEM) and challenged with 10(4) doses of the virus. Thereafter, the cultures were treated simultaneously with two-fold serial dilutions of the tested compound and incubated at 37 °C for 48 h. Molecular docking studies were done on the CVB4 2A proteinase enzyme using Molegro Virtual Docker software.

Results: The cytotoxicity (CC50), effective concentration (EC50) and the selectivity index (SI) values were determined. Based on their EC50 values, a number of the investigated compounds demonstrated weak to moderate activity relative to their parents. Accordingly, compounds 5-9, 11, 15-18, 21, 22, 24, 25, 27 and 28 were active against CVB4, and compounds 5 and 24 were active against HSV-1 and 2 in comparison to ribavirin and acyclovir, which were used as reference drugs.

Conclusion: The obtained results gave us some useful insights about the characteristic requirements for future trials to build up and design more active and selective antiviral 2-thioxo-benzo[g]quinazolin-4(3H)-one agents.Graphical abstractCompound 24 superimposed with Ribavirin in CV B4 2A Proteinase enzyme (PDB: 1Z8R) active site.

No MeSH data available.


Related in: MedlinePlus

Synthetic route for 2-thioxo-benzo[g]quinazolines (1–28)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4837545&req=5

Sch1: Synthetic route for 2-thioxo-benzo[g]quinazolines (1–28)

Mentions: We previously reported our findings regarding the antiviral activity of isoquinazoline and triazoloquinazoline derivatives. The results suggested that quinazolines can be good platform for designing a new antiviral agent [11–13]. Here, we are reporting the results of an antiviral investigation for a new series of 2-thioxo-benzo[g]quinazolines 1–28 (Table 1 and Scheme 1) [18]. The evaluation of the synthesized compounds 1–28 against HSV-1, HSV-2 and CVB4 was assessed in vitro using an MTT assay. Their cytotoxic effects were also evaluated. Results obtained from this screening showed that most of the compounds demonstrated antiviral activity, which ranged from weak through moderate to high effects, based on EC50 and SI values relative to their parent and reference drugs (Table 2). In accordance to the statistical analyses and in terms of SI as a marker for antiviral activity, all tested molecules have been classified into three groups: inactive- (SI < 2), active- (2 ≤ SI < 10) and very active-types (SI ≥ 10) [19]. Accordingly, compounds 5–9, 11, 15–18, 21, 22, 24, 25, 27 and 28 were active against CVB4. On the other hand, compound 5 has shown activity against HSV 1 and 2, while 24 was found to be active against HSV 1. It may be noticed that the tested molecules 5 and 9 showed significant levels of high activity against CVB4, with SI values of 6.27 and 5.77, whereas 15, 21 and 24 were less active (3.60, 3.73 and 3.85, respectively) with regard to ribavirin (16.38). However, 6, 7, 8, 11, 16, 17, 18, 22, 25, 27 and 28 exhibited moderate activity against CVB4, with SI values in the range of 2.05‒3.31. Moreover, compound 5 demonstrated good activity against HSV-1 and HSV-2 (SI = 4.28 and 5.18, respectively) and 24 was active against HSV-1 (SI = 2.61) in relation to ribavirin (41.93 and 24.69).Table 1


Molecular docking study and antiviral evaluation of 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives.

Al-Salahi R, Abuelizz HA, Ghabbour HA, El-Dib R, Marzouk M - Chem Cent J (2016)

Synthetic route for 2-thioxo-benzo[g]quinazolines (1–28)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837545&req=5

Sch1: Synthetic route for 2-thioxo-benzo[g]quinazolines (1–28)
Mentions: We previously reported our findings regarding the antiviral activity of isoquinazoline and triazoloquinazoline derivatives. The results suggested that quinazolines can be good platform for designing a new antiviral agent [11–13]. Here, we are reporting the results of an antiviral investigation for a new series of 2-thioxo-benzo[g]quinazolines 1–28 (Table 1 and Scheme 1) [18]. The evaluation of the synthesized compounds 1–28 against HSV-1, HSV-2 and CVB4 was assessed in vitro using an MTT assay. Their cytotoxic effects were also evaluated. Results obtained from this screening showed that most of the compounds demonstrated antiviral activity, which ranged from weak through moderate to high effects, based on EC50 and SI values relative to their parent and reference drugs (Table 2). In accordance to the statistical analyses and in terms of SI as a marker for antiviral activity, all tested molecules have been classified into three groups: inactive- (SI < 2), active- (2 ≤ SI < 10) and very active-types (SI ≥ 10) [19]. Accordingly, compounds 5–9, 11, 15–18, 21, 22, 24, 25, 27 and 28 were active against CVB4. On the other hand, compound 5 has shown activity against HSV 1 and 2, while 24 was found to be active against HSV 1. It may be noticed that the tested molecules 5 and 9 showed significant levels of high activity against CVB4, with SI values of 6.27 and 5.77, whereas 15, 21 and 24 were less active (3.60, 3.73 and 3.85, respectively) with regard to ribavirin (16.38). However, 6, 7, 8, 11, 16, 17, 18, 22, 25, 27 and 28 exhibited moderate activity against CVB4, with SI values in the range of 2.05‒3.31. Moreover, compound 5 demonstrated good activity against HSV-1 and HSV-2 (SI = 4.28 and 5.18, respectively) and 24 was active against HSV-1 (SI = 2.61) in relation to ribavirin (41.93 and 24.69).Table 1

Bottom Line: The cytotoxicity (CC50), effective concentration (EC50) and the selectivity index (SI) values were determined.Based on their EC50 values, a number of the investigated compounds demonstrated weak to moderate activity relative to their parents.Accordingly, compounds 5-9, 11, 15-18, 21, 22, 24, 25, 27 and 28 were active against CVB4, and compounds 5 and 24 were active against HSV-1 and 2 in comparison to ribavirin and acyclovir, which were used as reference drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451 Saudi Arabia.

ABSTRACT

Background: The persistent appearance of viral strains that causes a resistant viral infection has led to continuous trials for the design and development of novel antiviral compounds. Benzoquinazoline compounds have been reported to exhibit an interesting antiviral activity. This work aims to study and evaluate the antiviral activity of a newly prepared 2-thioxo-benzo[g]quinazolin-4(3H)-one series against herpes simplex (HSV-1 & 2) and coxsackievirus (CVB4).

Methods: The antiviral activity was performed using the MTT assay, in which Vero cells (obtained from the American Type Culture Collection, ATCC) were propagated in fresh Dulbecco's Modified Eagle's Medium (DMEM) and challenged with 10(4) doses of the virus. Thereafter, the cultures were treated simultaneously with two-fold serial dilutions of the tested compound and incubated at 37 °C for 48 h. Molecular docking studies were done on the CVB4 2A proteinase enzyme using Molegro Virtual Docker software.

Results: The cytotoxicity (CC50), effective concentration (EC50) and the selectivity index (SI) values were determined. Based on their EC50 values, a number of the investigated compounds demonstrated weak to moderate activity relative to their parents. Accordingly, compounds 5-9, 11, 15-18, 21, 22, 24, 25, 27 and 28 were active against CVB4, and compounds 5 and 24 were active against HSV-1 and 2 in comparison to ribavirin and acyclovir, which were used as reference drugs.

Conclusion: The obtained results gave us some useful insights about the characteristic requirements for future trials to build up and design more active and selective antiviral 2-thioxo-benzo[g]quinazolin-4(3H)-one agents.Graphical abstractCompound 24 superimposed with Ribavirin in CV B4 2A Proteinase enzyme (PDB: 1Z8R) active site.

No MeSH data available.


Related in: MedlinePlus