Synthetic routes and structure-activity relationships (SAR) of anti-HIV agents: A key review.

The worldwide increase of AIDS, an epidemic infection in constant development has an essential and still requires potent antiretroviral chemotherapeutic agents for reducing the integer of deaths caused by HIV. Thus, there is an urgent need for new anti-HIV drug candidates with increased strength, new targets, superior pharmacokinetic properties, and compact side effects. From this viewpoint, we first review present strategies of anti-HIV drug innovation and the synthesis of heterocyclic or natural compound as anti-HIV agents for facilitating the development of more influential and successful anti-HIV agents.

Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review.

At present more than 250 FDA approved chlorine containing drugs were available in the market and many pharmaceutically important drug candidates in pre-clinical trials. Thus, it is quite obvious to expect that in coming decades there will be an even greater number of new chlorine-containing pharmaceuticals in market. Chlorinated compounds represent the family of compounds promising for use in medicinal chemistry. This review describes the recent advances in the synthesis of chlorine containing heterocyclic compounds as diverse biological agents and drugs in the pharmaceutical industries for the inspiration of the discovery and development of more potent and effective chlorinated drugs against numerous death-causing diseases.

Pharmaceutical significance of azepane based motifs for drug discovery: A critical review.

Azepane-based compounds showed a variety of pharmacological properties, and its derivatives possess a high degree of structural diversity, and it is useful for the discovery of new therapeutic agents. The development of new less toxic, low-cost and highly active azepane-containing analogs is a hot research topic in medicinal chemistry. Now, more than 20 azepane-based drugs have been approved by FDA, and widely used to treat various types of diseases. This review highlights the recent developments of azepane-based compounds in a wide range of therapeutic applications, such as anti-cancer, anti-tubercular, anti-Alzheimer's disease, and antimicrobial agents, as well as, histamine H3 receptor inhibitors, α-glucosidase inhibitors, anticonvulsant drugs and other miscellaneous applications. We here briefly describe the structure-activity relationship (SAR) and molecular docking studies of potential bioactive compounds for future discovery of suitable drug candidates. It can serve as an inspiration for new ideas for design and development of less toxic and more powerful azepane-based drugs against numerous devastating diseases.

Multi-targeted dihydrazones as potent biotherapeutics.

Hydrazone compounds were considered as a useful moiety in drug design development. Therefore, these studies were aimed at the synthesis of new dihydrazones and were screened for their in vitro H+/K+-ATPase and anti-inflammatory activities. The results revealed that compounds 9 (22 ±â€¯0.62 µg/mL), 10 (26 ±â€¯0.91 µg/mL), 15 (24 ±â€¯0.44 µg/mL), 16 (28 ±â€¯0.63 µg/mL), 17 (12 ±â€¯0.38 µg/mL), 18 (14 ±â€¯0.47 µg/mL), 19 (26 ±â€¯0.54 µg/mL), 20 (16 ±â€¯0.41 µg/mL), 25 (06 ±â€¯0.68 µg/mL) and 26 (08 ±â€¯0.43 µg/mL) showed excellent H+/K+-ATPase activity and their IC50 value were lower than the standard drug Omerazole (48 ±â€¯0.12 µg/mL). Compounds 5 (28 ±â€¯0.65 µg/mL), 6 (24 ±â€¯0.61 µg/mL), 7 (28 ±â€¯0.64 µg/mL), 8 (26 ±â€¯0.45 µg/mL), 11 (30 ±â€¯0.74 µg/mL), 12 (28 ±â€¯0.40 µg/mL), 13 (32 ±â€¯0.24 µg/mL), 14 (30 ±â€¯0.55 µg/mL) and 21 (08 ±â€¯0.47 µg/mL), 22 (12 ±â€¯0.47 µg/mL), 23 (10 ±â€¯0.51 µg/mL) and 24 (14 ±â€¯0.84 µg/mL) showed better anti-inflammatory activity compared to standard indomethacin (44 ±â€¯0.15 µg/mL). The structure activity relationship (SAR) showed that, electron donating groups (OH, OCH3) favored the H+/K+-ATPase and antioxidants activity, whereas, electron withdrawing groups (F, Cl, Br and NO2) favored the anti-inflammatory activity. Furthermore, molecular docking study was performed to investigate the binding interactions of the most active analogs with the active site of H+/K+-ATPase enzyme. Compounds 25 (G-score = -9.063) and 26 (G-score = -8.977) showed the highest docking G-scores for H+/K+-ATPase inhibition activity.

Podophyllotoxin derivatives as an excellent anticancer aspirant for future chemotherapy: A key current imminent needs.

Cancer is one of the leading groups of threatened caused by abnormal state cell growth and second leading diseases involved in the major global death. To treat this, research looking for promising anticancer drugs from natural resource, or synthesized novel molecules by diverse group of scientists worldwide. Currently, drugs get into clinical practices and showing side effects with target actions which in turn leading to multidrug resistance unknowingly. Podophyllotoxin, a naturally occurring lignan and with hybrids have become one of the most attractive subjects due to their broad spectrum of pharmacological activities. Podophyllotoxin derivatives have been the centre of attention of extensive chemical amendment and pharmacological investigation in modern decades. Mainly, the innovation of the semi-synthetic anticancer drugs etoposide and teniposide has stimulated prolonged research interest in this structural phenotype. The present review focuses mainly onnew anticancer drugs from podophyllotoxin analogs, mechanism of action and their structure-activity relationships (SAR) as potential anticancer candidates for future discovery of suitable drug candidates.

Promising bactericidal approach of dihydrazone analogues against bio-film forming Gram-negative bacteria and molecular mechanistic studies.

Gram-negative members of the ESCAPE family are more difficult to treat, due to the presence of an additional barrier in the form of a lipopolysaccharide layer and the efficiency of efflux pumps to pump out the drugs from the cytoplasm. The development of alternative therapeutic strategies to tackle ESCAPE Gram-negative members is of extreme necessity to provide a solution to the cause of life-threatening infections. The present investigations demonstrated that compounds 17, 20, 25 and 26 possessing the presence of electron donating (OH and OCH3) groups on the phenyl rings are highly potent; whereas compounds 9, 10, 15, 16, 18, 33 and 36 showed moderate activity against Gram-negative bacteria. An excellent dose-dependent antibacterial activity was established compared to that of the standard antibiotic ampicillin. Significant anti-biofilm properties were measured quantitatively, showing optical density (O.D) values of 0.51 ± 015, 0.63 ± 0.20, 0.38 ± 0.07 and 0.62 ± 0.11 at 492 nm and the leakage of cellular components by the compounds, such as 17, 20, 25 and 26, increased the O.D. of respective treated samples compared to the control. In addition, the implication of experimental results is discussed in the light of the lack of survivability of planktonic bacteria and biofilm destruction in vitro. These results revealed the great significance of the development of a new generation of synthetic materials with greater efficacy in anti-biofilm properties by targeting to lock the bio-film associated protein Bap in Gram-negative bacteria.

Benzisoxazole: a privileged scaffold for medicinal chemistry.

The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds. The unique benzisoxazole scaffold also exhibits an impressive potential as antimicrobial, anticancer, anti-inflammatory, anti-glycation agents and so on. This review examines the state of the art in medicinal chemistry as it relates to the comprehensive and general summary of the different benzisoxazole analogs, their use as starting building blocks of multifarious architectures on scales sufficient to drive human drug trials. The number of reports describing benzisoxazole-containing highly active compounds leads to the expectation that this scaffold will further emerge as a potential candidate in the field of drug discovery.

Synthesis and SAR studies of potent H(+)/K(+)-ATPase inhibitors of quinazolinone-Schiff's base analogues.

A series of quinazolinone derived Schiff base derivatives 7-36 were synthesized and characterized by analytical and spectroscopic techniques. The synthesized analogues were screened for their in vitro H(+)/K(+)-ATPase inhibition. Most of the compounds showed excellent activity, compared to that of omeprazole, a reference drug. In particular, hydroxy and methoxy derivatives 13-24 were the most active compounds possessing a significant increase for different substituents on the benzene ring thus, contributing positively to gastric H(+)/K(+)-ATPase inhibition. Preliminary structure-activity relationship revealed that the compounds 13-24 with electron donating moiety (OH, OCH3) were found to be excellent activity and compounds 9-12 and 25-36 with electron withdrawing moiety (Cl, F, NO2 and Br) were found to be least antiulcer 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 microM against the positive control, Rutin, with IC50 = 41.9 microM. Thus, the title compounds represent novel class of potent antiglycating 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.