Substituent-Dependent Absorption Spectra, Electrochemical and Antiproliferative Activity Studies of Some 3-(4-(Benzyloxy)phenyl)-5-(4-methoxyphenyl)-1-(substitutedphenyl)formazans
CHEMISTRYSELECT
Authors: Turkoglu, Gulsen; Akkoc, Senem
Abstract
We have reported the effect of electron donating and withdrawing substituents on absorption and electrochemical properties of formazan derivatives as well as antiproliferative activity. New formazans F2 and F4 bearing electron donating subunits have been synthesized, and characterized via elemental analysis and various spectroscopic techniques. The substituent effects and solvatochromic of formazan derivatives F2-F5 having different substituents on 1-phenyl ring in eleven solvents were investigated by absorption spectroscopy. Whilst their absorption bands are only slightly dependent on the polarities of solvents, the considerable alteration was detected by modifying the electronic characteristic and positions of the substituents. Then, the antiproliferative activity of all compounds was investigated in four cancer cell lines using MTT and XTT assay methods. The IC50 values of F2 and F4, having electron donating methoxy and methyl subunits were obtained in the ranges of 10.60 and 21.53 mu M in DLD-1 and HepG2 cell lines. Our study demonstrates that F2 and F4 are more active than the positive control drug used.
Natural phyto, compounds as possible noncovalent inhibitors against SARS-CoV2 protease: computational approach
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Authors: Ogidigo, Joyce Oloaigbe; Iwuchukwu, Emmanuel A.; Ibeji, Collins U.; Okpalefe, Okiemute; Soliman, Mahmoud E. S.
Abstract
At present, there is no cure or vaccine for the devastating new highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected people globally. Herein, we identified potent phytocompounds from two antiviral plants Momordica charantia L. and Azadirachta indica used locally for the treatment of viral and parasitic infections. Structure-based virtual screening and molecular dynamics (MD) simulation have been employed to study their inhibitory potential against the main protease (M-pro) SARS-CoV-2. A total of 86 compounds from M. charantia L. and A. indica were identified. The top six phytocompounds; momordicine, deacetylnimninene, margolonone, momordiciode F2, nimbandiol, 17-hydroxyazadiradione were examined and when compared with three FDA reference drugs (remdesivir, hydroxychloroquine and ribavirin). The top six ranked compounds and FDA drugs were then subjected to MD simulation and pharmacokinetic studies. These phytocompounds showed strong and stable interactions with the active site amino acid residues of SARS-CoV-2 Mpro similar to the reference compound. Results obtained from this study showed that momordicine and momordiciode F2 exhibited good inhibition potential (best MMGBA-binding energies; -41.1 and -43.4 kcal/mol) against the M-pro of SARS-CoV-2 when compared with FDA reference anti-viral drugs (Ribavirin, remdesivir and hydroxychloroquine). Per-residue analysis, root mean square deviation and solvent-accessible surface area revealed that compounds interacted with key amino acid residues at the active site of the enzyme and showed good system stability. The results obtained in this study show that these phytocompounds could emerge as promising therapeutic inhibitors for the M-pro of SARS-CoV-2. However, urgent trials should be conducted to validate this outcome. Communicated by Ramaswamy H. Sarma