D. M. Suyoga Vardhan

Inhibition of protein glycation by urea and thiourea derivatives of glycine/proline conjugated benzisoxazole analogue – Synthesis and structure–activity studies

Synthesis of a new series of urea/thiourea derivatives of Gly/Pro conjugated benzisoxazole has been reported. Structure of the compounds was characterized by physical and spectroscopical data and has been screened for their in vitro antiglycation activity. Several compounds showed promising activity with IC(50) < 5 μM compared to standard rutin (IC(50) = 41.9 μM). Further, it was found that compounds containing methoxy and bromine substituents have exerted highly potent activity. Thus, the title compounds represent novel class of potent antiglycating agents.

Design and synthesis of amino acids-conjugated heterocycle derived ureas/thioureas as potent inhibitors of protein glycation

Protein glycation is believed to play an important role in the development of long-term disorders associated with diabetic complications. In view of the wide occurrence of advanced glycation end products (AGE’s) and the oxidative stress derived from them in a variety of diabetic complications, it would be of great interest to identify and develop AGE inhibitors. In this study, synthesis and in vitro antiglycation activity of a small library of forty urea/thiourea derivatives of Phe/Tyr/Glu/Lys-benzisoxazole hybrids are reported. Structures of the compounds were confirmed by IR, NMR, mass spectrometry, and elemental analysis. Most of the title compounds exhibited promising activity. Best antiglycation activity was found for Tyr analogue with methoxy group as a substituent particularly at the para position with IC50 value of 1.9 μM against the positive control, Rutin, with IC50 = 41.9 μM. Thus, the title compounds represent novel class of potent antiglycating agents.

A correlation study of biological activity and molecular docking of Asp and Glu linked bis-hydrazones of quinazolinones

The present investigation involves the synthesis and spectroscopic and biological activity studies of the bis-hydrazones of quinazolinones derived from aspartic acid and glutamic acid. The antioxidant activities of the compounds were evaluated using DPPH, DMPD and ABTS radical scavenging assays whose results revealed that the IC50 of compounds 6, 7, 11, 12, 20, 21, 25 and 26 was lower than those of the standard references. The anti-inflammatory activity was evaluated with a haemolysis assay using a human blood erythrocytes suspension and the results demonstrated that compounds 8, 9, 13, 14, 22, 23, 27 and 28 were excellent anti-inflammatory agents. In addition, the antibacterial and antifungal activities against various clinical pathogens of human origin revealed that compounds 7, 9, 12, 14, 21, 23, 26 and 28 possessed potent antimicrobial properties. Furthermore, to understand the correlation between biological activity and drug–receptor interaction, molecular docking was performed on the active sites of tyrosine kinase (PDB ID: 2HCK), cyclooxygenase-2 (PDB ID: 1CX2) and glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) which showed good binding profiles with the targets that can potentially hold the title compounds. The correlation study revealed that compounds containing EDGs (–OH, –OCH3) were excellent antioxidants, compounds with EWGs (–Cl, –NO2) exhibited good anti-inflammatory activity and compounds bearing –OH and –NO2 groups were very good antimicrobials.

Urea and Thiourea Derivatives of Dipeptides Conjugated Piperazine Analogue as A New Class of AGE’s Inhibitors: Synthesis and Molecular Docking Studies

A novel class of urea and thiourea derivatives of dipeptides conjugated 2, 3-dichlorophenyl piperazine were synthesized and evaluated for their AGEs inhibition capacity. Antiglycation assay was performed by assessing fluorescence spectrum (exitation 370 nm), and change in fluorescence intensity (to emission 440 nm), based on AGEs were monitored by using spectrofluorimeter. Our results indicate that fluoro containing dipeptide-PZN derivatives have shown excellent curative potential. Interestingly, compounds 6, 7, 14, 15, 22, 23, 30 and 31 have shown excellent potency with IC50 values 13.5 ± 0.77, 8.0 ± 0.25, 14.5 ± 0.92, 7.8 ±0.44, 9.1 ± 0.41, 3.1 ± 0.45, 9.2 ± 0.80 and 2.5 ± 0.55, compared to the standard, rutin 41.9 μM. From our studies, we may draw certain conclusions like Lys containing dipeptides may serve as good antiglycating agents. On the other hand, its felt worthy to consider substitutions particularly at para position for the increase in potency. The IC50 values of the compounds were compared with the glide scores from the molecular studies. It was observed that the main interaction force of compounds with the active site was hydrophobic. The IC50 values and glide scores have exhibited better correlation. Thus, this synthetic novel urea and thioureas of dipeptide containing compounds may lead potent antiglycating agents.