Abstract
Background: HIV is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) play an important role in the treatment of AIDS. Although, many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Methods: The best features of available NNRTIs were taken into account for the design of novel inhibitors. PASS (Prediction of activity spectra for substances) prediction program and molecular docking studies for the selection of designed compounds were used for the synthesis. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay. Results: The evaluation of HIV-1 RT inhibitory activity revealed that seven compounds have significantly lower ΙC50 values than nevirapine (0.3 μΜ). It was observed that the activity of compounds depends not only on the nature of substituent and it position in benzothiazole ring but also on the nature and position of substituents in benzene ring. Conclusion: Twenty four of the tested compounds exhibited inhibitory action lower than 4 μΜ. Seven of them showed better activity than nevirapine, while three of the compounds exhibited IC50 values lower than 5 nM. Two compounds 9 and 10 exhibited very good inhibitory activity with IC50 1 nM.
Highlights
Acute Immunodeficiency Syndrome (AIDS) is a result of the infection and destruction ofT-lymphocytes by the human immunodeficiency virus (HIV)
It is known that HIV-1 reverse transcriptase (HIV-1 RT) has a flexible structure that contains two binding domains
The active site characterized by the catalytic triad of Asp110, Asp185 and Asp186 residues, where the deoxynucleoside triphosphates are bound by the physiological process, and an allosteric site of nucleoside reverse transcriptase inhibitors (NNRTIs) about 10 Å away from the active site
Summary
Acute Immunodeficiency Syndrome (AIDS) is a result of the infection and destruction ofT-lymphocytes by the human immunodeficiency virus (HIV). Research for the development of novel NNRT inhibitors still continues as the virus develops resistant strains, limiting their use. Among the approved by FDA compounds are several heterocyclic compounds such as benzoxazin-2-one (etravirine), dipirydo [1,4] diazepine-6-one (etravirin) [4], piperazine and indolyl (delaverdine) moieties [5,6] Except of these drugs many other molecules have been found to display RT inhibitory action [7,8,9,10,11,12,13], among which are: benzothiazine dioxides [14], N1,N3-disubstituted uracils [15], Molecules 2019, 24, 3821; doi:10.3390/molecules24213821 www.mdpi.com/journal/molecules. Many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
