Podcast | In Silico Appraisal, Synthesis, Antibacterial Screening and DNA Cleavage for 1,2,5-thiadiazole Derivative

Author(s): Suraj N. Mali*, Sudhir Sawant, Hemchandra K. Chaudhari*, Mustapha C. Mandewale


Graphical Abstract:



Background: Thiadiazole not only acts as “hydrogen binding domain” and “two-electron donor system” but also as constrained pharmacophore.

Methods: The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1, 2,5-thiadiazol-3-yl) oxy) propyl) amino)- 2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology involves preparation of 4-morpholino-1, 2,5-thiadiazol-3-ol by hydroxylation of 4-(4-chloro-1, 2,5-thiadiazol-3-yl) morpholine followed by condensation with 2-(chloromethyl) oxirane to afford 4-(4-(oxiran-2-ylmethoxy)-1,2,5-thiadiazol- 3-yl) morpholine. Oxirane ring of this compound was opened by treating with 2-amino-2-methyl propan-1- ol to afford the target compound TML-Hydroxy. Structures of the synthesized compounds have been elucidated by NMR, MASS, FTIR spectroscopy.

Results: The DSC study clearly showed that the compound 4-maleate salt is crystalline in nature. In vitro antibacterial inhibition and little potential for DNA cleavage of the compound 4 were explored. We extended our study to explore the inhibition mechanism by conducting molecular docking, ADMET and molecular dynamics analysis by using Schrödinger. The molecular docking for compound 4 showed better interactions with target 3IVX with docking score of -8.508 kcal/mol with respect to standard ciprofloxacin (docking score= -3.879 kcal/mol). TML-Hydroxy was obtained in silico as non-carcinogenic and non-AMES toxic with good percent human oral absorption profile (69.639%). TML-Hydroxy showed the moderate inhibition against Mycobacteria tuberculosis with MIC 25.00 μg/mL as well as moderate inhibition against S. aureus, Bacillus sps, K. Pneumoniae and E. coli species.

Conclusion: In view of the importance of the 1,2,5-thiadiazole moiety involved, this study would pave the way for future development of more effective analogs for applications in medicinal field. For article details, please visit: http://www.eurekaselect.com/169670/article


Highlighted Article – Update on Nitazoxanide – Current Drug Discovery Technologies

CDDT-Articles_14-4-Anshul Shakya

To access this article, please visit: http://www.eurekaselect.com/154522

Press Release for EurekAlert! Bactericidal activity of usnic acid-loaded electrospun fibers


The development of antibiotics generated a revolution in the way we look and treat bacterial infections. In spite of the initial success, new problems came along and raised allergic reactions, bacterial resistance and ecological problems. These consequences have encouraged the research of alternative solutions based on sustainable sources. In this way, antibacterial agents that do not comprise metals or synthetic molecules is appealing. Among those alternatives, we found the (+)- usnic acid, a strong lichen metabolite, that has been progressively applied as active material in commercial products (such as creams, toothpaste, deodorant and sunscreen). These products take advantage of antiviral (Influenza A), antimicrobial, antifungi, anti-inflammatory, antiproliferative, analgesic, antiprotozoal and antipyretic properties of this natural product. The aggregation level of active material represents an important aspect to be circumvented to optimize the activity of usnic acid derivatives. In this work, it is proposed the novelty related with encapsulation of usnic acid in electrospun fibers of poly (vinyl pyrrolidone) and Eudragit L -100. This process favors the homogeneous distribution of active material in beads-free electrospun fibers, minimizing the aggregation level, providing reasonable surface area for diffusion of material along fiber walls and contributing to massive production of active available surface. An additional advantage is offered by loaded enteric electrospun fibers, that favors the development of new pH-controlled release antibacterial materials. The effective bactericidal activity of usnic acid was verified against different bacteria in a time dependent controlled diffusion process in which usnic acid acquires a controlled release rate from polymeric matrix (inhibition halo measurement reveals convenient activity of usnic acid). This property can be conveniently explored as a secondary therapy in the diabetics wound healing treatment due to the strong mechanical properties of fibers and adequate release profile of usnic acid.

Reference: Araujo, E.; et al (2016). Bactericidal Activity of Usnic Acid-Loaded Electrospun Fibers. Recent Pat Nanotechnol., DOI: 10.2174/1872210510666160517160144

For more information about this article, please visit: http://benthamscience.com/journals/recent-patents-on-nanotechnology/volume/10/issue/3/page/252/

Podcast: “1-R-2-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)etanon(ol)s: Synthesis, Bioluminescence Inhibition, Molecular Docking Studies, Antibacterial and Antifungal Activities”

Author: Lyudmyla M. Antypenko, Sergiy I. Kovalenko, Oleksandr V. Karpenko, Andrew M. Katsev, Volodymyr P. Novikov and Natalia S Fedyunina

For article details, visit: http://benthamscience.com/journals/current-computer-aided-drug-design/volume/12/issue/1/page/29/

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Is Your Favourite “Antibacterial” Product Raising The Next Best Superbug?

If we measure the commercial value of any skin cleansing product these days, it has got to have a tagline against the horrors of nasty pathogens. Especially, the hand hygiene products are advertised as if the presence of any type of bacteria is injurious to one’s good health. Hence, a bold announcement of “antibacterial” is needed for high sales volume of the product. This, however, is being questioned and disproved by the scientific community; furiously searching for an antidote to superbug. In fact, there is no evidence that antibacterial soaps clean better than any regular soap available in the market.

According to some researchers, the use of antibacterial soaps is causing the rise of “superbugs” and putting a question mark at the effectiveness of these microbe-hunting soaps which have chemicals that are contributing to the formation of mutant bugs. The most popular among such antibacterial agents is the triclosan – a compound that was originally used to scrub the hospital floors.

“Triclosan has a specific inhibitory target in bacteria similar to some antibiotics,” explained Allison Aiello; the epidemiologist, to Coco Ballantyne at Scientific American. Over time, the bug population exposed to triclosan develops the ability to endure and cross-resist the antibacterial aspect; causing the growth of superbugs.

In 2014, Minnesota approved a law that made it illegal to sell any products containing triclosan by 2017. Yet, in 75% of all the antibacterial products, such as, surface cleaners, detergents, toothpastes, and soaps; triclosan is still being used as a key ingredient in their current formulas. The chemical, however, doesn’t put any harmful effects on human enzymes – hence, making it safe for common use. If you are one of the harsh antimicrobial hand wash and hand sanitizer fanatics, it’s probably high time to reduce your reliance on them and trying alternative products such as organic soaps and environmental friendly cleaners that don’t contain harmful ingredients like triclosan, triclocarbon, lye, chlorine, ammonia, etc.



BSP Journal: Recent Patents on Anti-Infective Drug Discovery

ImageVolume 8 – Number 3

– Topical Antimicrobials for Burn Infections – An Update

Author(s): Mert Sevgi, Ani Toklu, Daniela Vecchio and Michael R. Hamblin

Affiliation: BAR414, 40 Blossom Street, Boston MA 02114, USA.


The relentless rise in antibiotic resistance among pathogenic bacteria and fungi, coupled with the high susceptibility of burn wounds to infection, and the difficulty of systemically administered antibiotics to reach damaged tissue, taken together have made the development of novel topical antimicrobials for burn infections a fertile area of innovation for researchers and companies. We previously covered the existing patent literature in this area in 2010, but the notable progress made since then, has highlighted the need for an update to bring the reader up to date on recent developments. New patents in the areas of topically applied antibiotics and agents that can potentiate the action of existing antibiotics may extend their useful lifetime. Developments have also been made in biofilm-disrupting agents. Antimicrobial peptides are nature’s way for many life forms to defend themselves against attack by pathogens. Silver has long been known to be a highly active antimicrobial but new inorganic metal derivatives based on bismuth, copper and gallium have emerged. Halogens such as chlorine and iodine can be delivered by novel technologies. A variety of topically applied antimicrobials include chitosan preparations, usnic acid, ceragenins and XF porphyrins. Natural product derived antimicrobials such as tannins and essential oils have also been studied. Novel techniques to deliver reactive oxygen species and nitric oxide in situ have been developed. Light-mediated techniques include photodynamic therapy, ultraviolet irradiation, blue light, low-level laser therapy and titania photocatalysis. Passive immunotherapy employs antibodies against pathogens and their virulence factors. Finally an interesting new area uses therapeutic microorganisms such as phages, probiotic bacteria and protozoa to combat infections.


– Novel Quercetin Glycosides as Potent Anti-MRSA and Anti-VRE Agents

Author(s): Abugafar M.L. Hossion and Kenji Sasaki

Affiliation: The University of Pittsburgh, 100 Technology Drive, Pittsburgh, PA 15218, USA.


Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections (Threat report 2013). Vancomycin is an FDA approved antibiotic and is growing importance in the treatment of hospital infections, with particular emphasis on its value to fight against methicillin-resistant Staphylococcus aureus (MRSA). The increasing use of vancomycin to treat infections caused by the Gram-positive MRSA in the 1970s selected for drug-resistant enterococci, less potent than staphylococci but opportunistic in the space vacated by other bacteria and in patients with compromised immune systems. The dramatic rise of antibiotic-resistant bacteria over the past two decades has stressed the need for completely novel classes of antibacterial agents. This paper reports the recent patent review on the strategy for finding novel quercetinglycoside type antibacterial agents against vancomycin-resistant bacterial strains.


– The Mechanism by which the Phenothiazine Thioridazine Contributes to Cure Problematic Drug-Resistant Forms of Pulmonary Tuberculosis: Recent Patents for “New Use”

Author(s): Leonard Amaral, Ana Martins, Gabriella Spengler, Attila Hunyadi and Joseph Molnar

Affiliation: Travel Medicine, Centro de Malária Doenças Tropicais, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1349-008 Lisbon, Portugal.


At this moment, over half million patients suffer from multi-drug resistant tuberculosis (MDR-TB) according to the data from the WHO. A large majority is terminally ill with essentially incurable pulmonary tuberculosis. This herein mini-review provides the experimental and observational evidence that a specific phenothiazine, thioridazine, will contribute to cure any form of drug-resistant tuberculosis. This antipsychotic agent is no longer under patent protection for its initial use. The reader is informed on the recent developments in patenting this compound for “new use” with a special emphasis on the aspects of drug-resistance. Given that economic motivation can stimulate the use of this drug as an antitubercular agent, future prospects are also discussed.


Parenteral Patent Drug S/GSK1265744 has the Potential to be an Effective Agent in Pre-Exposure Prophylaxis Against HIV Infection

Author(s): Huda Taha, James Morgan, Archik Das and Satyajit Das

Affiliation: Department of HIV Medicine, Coventry & Warwickshire Partnership Trust, United Kingdom.


The continuing HIV epidemic has driven advancements in antiretroviral therapy. New therapeutic targets have been identified over the past years, one of which has been the Integrase enzyme. This is responsible for integrating HIV pro-DNA into the host cell genome and has proved a successful drug target.


Efforts have also been made to improve the pharmacokinetic parameters of current drug therapy and utilise these techniques in maximising drug therapeutic effect whilst minimising adverse events. An exciting example of new technologies is that of nanotechnology where drugs can be specifically targeted to certain tissues and drug delivery can be improved by utilising biological molecules and structures.

Pre-exposure prophylaxis is also an area of much interest currently both on an individual and population level. Compliance is however a major issue with daily medication to prevent HIV acquisition as has been demonstrated with contraceptive agents. However if long acting compounds can be developed, compliance can be improved.

The patent drug currently being developed through nanotechnology as an analogue of Dolutegravir, GSK1265744 LAP (Long Acting Parenteral) has shown promise as a Long Acting Integrase Inhibitor with potential action both as a therapeutic agent but also in pre-exposure prophylaxis. The favourable pharmacokinetic profile and therapeutic efficacy in comparison to other compounds of the same class demonstrate it to be a promising advance. However given current limitations in study material, further randomised studies with long term follow up are required to fully evaluate the value of the patent drug GSK1265744 LAP in action in both seropositive and seronegative individuals.

For details on the journal, please visit: Recent Patents on Anti-Infective Drug Discovery

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