R. Suhas

Urea/thiourea derivatives of quinazolinone-lysine conjugates: synthesis and structure-activity relationships of a new series of antimicrobials.

Synthesis of a series of urea/thiourea/acetamide/sulphonamide derivatives of quinazolinones conjugated lysine has been reported. Structures of the products have been determined by standard spectroscopical studies. All the compounds have been screened for their antibacterial studies and structure-activity relationship has been developed. The activity profile revealed that the compounds containing urea and thiourea functionalities along with fluoro group have exerted a highly potent activity. Thus, the title compounds represent a novel class of potent antimicrobial agents.

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.

Synthesis of uriedo and thiouriedo derivatives of peptide conjugated heterocycles - A new class of promising antimicrobials.

Forty five new derivatives of ureas and thioureas were synthesized by the reaction of peptide conjugated heterocycles with isocyanates and isothiocyanates respectively. All the compounds have been characterized by IR, (1)H NMR, mass and elemental analysis. The compounds were evaluated for their ability to inhibit the growth of a panel of microorganisms and all the synthesized compounds displayed an excellent antimicrobial activity. From structure-activity relationship studies, it was apparent that thioureas infact is slightly more active than ureas. Also, substituents on the phenyl ring of the title compounds play a key role in the activity. Further, compound 40 is nearly twenty times more potent than the standard used. These results present a platform for the further studies in this line.

Structure-Based Rationale Design and Synthesis of Aurantiamide Acetate Analogues – Towards a New Class of Potent Analgesic and Anti-inflammatory Agents

A series of new aurantiamide acetate analogues were synthesized by modifying its N‐terminal substitution and the amino acid residue. The structure of all these compounds was established on the basis of analytical and spectral studies. All the new derivatives were evaluated in vivo for their analgesic activity by tail flick method in mice and anti‐inflammatory activity against carrageenan‐induced oedema in albino rats at different doses (25, 50 and 100 mg/kg body weight). All the compounds exhibited significant pharmacological activity with no ulcerogenic liability. In particular, pentapeptides and tricosamers (30 amino acids) containing analogues have demonstrated high potency than the reference standards. These compounds hold promise for further development.

Ureas/Thioureas of Benzo[d]isothiazole Analog Conjugated Glutamic Acid: Synthesis and Biological Evaluation.

A series of urea and thiourea derivatives of glutamic acid conjugated to 3‐(1‐piperazinyl)‐1,2‐benzisothiazole were synthesized, spectroscopically characterized, and evaluated for their in vitro antiglycation and urease inhibitory activities. Preliminary screening of the synthesized compounds 1–35 showed significant results. Amongst these, compounds 17–21 and 30–35 bearing fluoro and methoxy substituents, respectively, exhibited inhibitory potency greater than the reference standards. Hence, they may serve as new lead compounds for further development.

Design and synthesis of tryptophan containing peptides as potential analgesic and anti-inflammatory agents.

A new series of smaller peptides with tryptophan at C‐terminal and varying N‐protected amino acids/peptides were designed, synthesized and characterized by analytical and spectroscopic techniques. Analgesic and anti‐inflammatory properties of these peptides were carried out in vivo using tail‐flick method and carrageenan‐induced paw edema method, respectively, at different doses and different time intervals. Most of the peptides synthesized displayed enhanced activity, and particularly tetra and hexapeptides 29–31 were found to be even more potent than the reference standards used. Moreover, some peptides have exhibited promising activity even after 24 h of administration, whereas the reference standards were active only up to 3 h. Further, the compounds did not present any ulcerogenic liability. Copyright

tert-Butyl 1,5-bis(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-1,5-dioxopentan-2-ylcarbamate urea/thiourea derivatives as potent H+/K+-ATPase inhibitors

Amino acids are known to possess variable efficacy against ulceration. Considering the good antiulcer activity of amino acids, a series of urea/thiourea derivatives of glutamic acid conjugated benzisothiazole analogue 3a-u with various substituents on aryl ring were synthesized, spectroscopically characterized and evaluated for in vitro H(+)/K(+)-ATPase inhibition. Majority of the compounds possessed potency compared to that of omeprazole, a reference drug. In particular, methoxy derivatives 3p-u were the most active compounds possessing a significant 15-fold increase for para substituent thus, contributing positively to gastric H(+)/K(+)-ATPase inhibition.

Synthesis and SAR studies of urea and thiourea derivatives of gly/pro conjugated to piperazine analogue as potential AGE inhibitors.

Synthesis of a series of urea and thiourea derivatives of glycine and proline conjugated to 2,3-dichlorophenyl piperazine has been reported. The structures were confirmed by physical and spectroscopical measurements followed by characterization of antiglycation activity. All synthesized compounds were able to inhibit protein glycation, particularly halogen containing derivatives without preference of oxygen or sulphur at the urea function. The best analogues are nearly 20 fold (< 5 µM) more potent than the reference standard, rutin (41.9 µM).

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.

Synthesis of Quinazolinone Conjugated Shorter Analogues of Bactenecin7 as Potent Antimicrobials

A series of shorter peptide analogues of Bactenecin7 (RP, PRP, GPRP and RPRP) were synthesized and conjugated to 3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanoic acid to study the effect of conjugation. All the peptides and their conjugates were characterized by analytical and spectroscopic techniques. The synthesized compounds viz., peptides, heterocyclic conjugates and the hydrogenolyzed products were evaluated for antimicrobial activity against a panel of pathogens. The results revealed that all the conjugates have shown enhanced activity than their counterparts. Further, hydrogenolyzed tetrapeptide conjugates (10 and 13) have exerted highly potent activity nearly 3-4 times than the standard drugs used.