Benzothiazoles: From recent advances in green synthesis to anti-cancer potential

According to World Health Organization Cancer is the second leading cause of death worldwide which accounted for an estimated 10.0 million deaths in 2020. Globally, the cancer burden is continuously growing, and it exerts tremendous physical, emotional, and financial strain on individuals, families, communities, and health systems. Looking at the stakes, researchers are vigorously trying to develop new anticancer agents. Recently, benzothiazole is emerging as one of the most active and interesting ingredients in the treatment against carcinoma cells but the problem lies with the complex multi-step processes implemented in pharmaceutical industries to synthesize target molecules as they produce a tremendous amount of waste. To prevail over the concerns of environmental agencies now focus has been shifted towards the synthesis of drugs using green reaction conditions. This work covers the recent advances in the green synthesis of benzothiazole scaffold along with its anticancer potential.     

Synthesis and Characterization of Amphiphilic Poly(ethylene oxide)‐block‐poly(hexyl methacrylate) Copolymers

We describe the preparation of amphiphilic diblock copolymers made of poly(ethylene oxide) (PEO) and poly(hexyl methacrylate) (PHMA) synthesized by anionic polymerization of ethylene oxide and subsequent atom transfer radical polymerization (ATRP) of hexyl methacrylate (HMA). The first block, PEO, is prepared by anionic polymerization of ethylene oxide in tetrahydrofuran. End capping is achieved by treatment of living PEO chain ends with 2‐bromoisobutyryl bromide to yield a macroinitiator for ATRP. The second block is added by polymerization of HMA, using the PEO macroinitiator in the presence of dibromobis(triphenylphosphine) nickel(II), NiBr₂(PPh₃)₂, as the catalyst. Kinetics studies reveal absence of termination consistent with controlled polymerization of HMA. GPC data show low polydispersities of the corresponding diblock copolymers. The microdomain structure of selected PEO‐block‐PHMA block copolymers is investigated by small angle X‐ray scattering experiments, revealing behavior expected from known diblock copolymer phase diagrams.

SAXS diffractograms of PEO‐block‐PHMA diblock copolymers with 16, 44, 68 wt.‐% PEO showing spherical (A), cylindrical (B), and lamellae (C) morphologies, respectively.     

Seasonal Plasticity in the Peptide Neuronal Systems: Potential Roles of Gonadotrophin‐Releasing Hormone,Gonadotrophin‐Inhibiting Hormone,Neuropeptide Y and Vasoactive Intestinal Peptide in the Regulation of the Reproductive Axis in Subtropical Indian Weaver Birds

Two experiments examined the expression of gonadotrophin‐releasing and inhibiting hormones (GnRH‐I, GnRH‐II and GnIH), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) in subtropical Indian weaver birds, which demonstrate relative photorefractoriness. Experiment 1 measured peptide expression levels in the form of immunoreactive (‐IR) cells, percentage cell area and cell optical density in the preoptic area (GnRH‐I), midbrain (GnRH‐II), paraventricular nucleus (GnIH), mediobasal hypothalamus [dorsomedial hypothalamus (DMH), infundibular complex (INc), NPY and VIP] and lateral septal organ (VIP) during the progressive, breeding, regressive and nonbreeding phases of the annual reproductive cycle. GnRH‐I was decreased in the nonbreeding and VIP was increased in INc in the breeding and regressive states. GnRH‐II and NPY levels did not differ between the testicular phases. Double‐labelled immunohistochemistry (IHC) revealed a close association between the GnRH/GnIH, GnRH/NPY, GnRH/VIP and GnIH/NPY peptide systems, implicating them interacting and playing roles in the reproductive regulation in weaver birds. Experiment 2 further measured these peptide levels in the middle of day and night in weaver birds that were maintained under short days (8 : 16 h light /dark cycle; photosensitive), exposed to ten long days (16 : 8 h light /dark cycle; photostimulated) or maintained for approximately 2 years on a 16 : 8 h light /dark cycle (photorefractory). Reproductively immature testes in these groups precluded the possible effect of an enhanced gonadal feedback on the hypothalamic peptide expression. There were group differences in the GnRH‐I (not GnRH‐II), GnIH, NPY and VIP immunoreactivity, albeit with variations in immunoreactivity measures in the present study. These results, which are consistent with those reported in birds with relative photorefractoriness, show the distribution and possibly a complex interaction of key neuropeptides in the regulation of the annual reproductive cycle in Indian weaver birds.     

Cryptotanshinone protects against oxidative stress in the paraquat-induced Parkinson's disease model

Parkinson's disease (PD) is a common neurodegenerative disorder associated with striatal dopaminergic neuronal loss in the Substantia nigra. Oxidative stress plays a significant role in several neurodegenerative diseases. Paraquat (PQ) is considered a potential neurotoxin that affects the brain leading to the death of dopaminergic neurons mimicking the PD phenotype. Various scientific reports have proven that cryptotanshinone possesses antioxidant and anti-inflammatory properties. We hypothesized that cryptotanshinone could extend its neuroprotective activity by exerting antioxidant effects. This study was designed to evaluate the effects of cryptotanshinone in both cellular and animal models of PQ-induced PD. Annexin V-PI double staining and immunoblotting were used to detect apoptosis and oxidative stress proteins, respectively. Reactive oxygen species kits were used to evaluate oxidative stress in cells. For in vivo studies, 18 B6 mice were divided into three groups. The rotarod data revealed the motor function and immunostaining showed the survival of TH+ neurons in SNpc region. Our study showed that cryptotanshinone attenuated paraquat-induced oxidative stress by upregulating anti-oxidant markers in vitro, and restored behavioral deficits and survival of dopaminergic neurons in vivo, demonstrating its therapeutic potential.     

Competing HB acceptors: an extensive NMR investigations corroborated by single crystal XRD and DFT calculations

A series of N-benzoylanthranilamide derivatives have been synthesized with the substitution of competitive HB acceptors and investigated by NMR spectroscopy and single crystal XRD. The interesting rivalry for HB acceptance between C O and X (F or OMe) is observed in the investigated molecules which leads to an unusual increase in the electron density at the site of one of the NH protons, reflecting in the high field resonance in the ¹H NMR spectrum. The NMR experimental findings and single crystal XRD are further reinforced by the DFT studies.

A series of N-benzoylanthranilamide derivatives have been synthesized with the substitution of competitive HB acceptors and investigated by NMR spectroscopy and single crystal XRD.     

Surgeons’ preferences and practice patterns regarding intraoperative frozen section during partial nephrectomy

PurposeIntraoperative frozen section (FS) evaluation for tumor margin during partial nephrectomy (PN) is a matter of controversy in urologic oncology. We evaluated the preferences and practice patterns of urologists regarding intraoperative FS during PN.MethodsA 17-item questionnaire was designed to collect information on surgeons’ preferences and practice patterns regarding FS during PN. The survey was sent to the members of the Society of Urologic Oncology and Endourological Society.ResultsA total of 197 responses were received. Overall, 69% and 58% of respondents chose to obtain FS (always or sometimes) during open PN (OPN) and laparoscopic PN (LPN), respectively. There was a strong correlation between the surgeons’ preferences during OPN and LPN. Younger surgeons are less likely to obtain FS during OPN. For surgeons who did not routinely obtain FS, “confidence about complete resection” was the most common reason (79%), followed by “no change in management with positive margins” (35%). Most surgeons (75%) believed the margins to be negative, if surgical margin was free of tumor microscopically by a single cell layer. Older surgeons considered negative margins to be free of tumor microscopically by ≥5 mm. Overall, 54% and 42% of respondents would repeat FS for positive microscopic margins during OPN and LPN, respectively. Of the respondents, 95% would not recommend additional treatment for positive margins on final pathology.ConclusionDespite recent literature pointing to low clinical utility of FS, most surgeons still obtain FS during PN. Older surgeons tend to obtain FS more often. Fellowship training and practice type do not appear to influence preferences and practice patterns in regard to FS.     

Distinguishing classical papillary thyroid microcancers from follicular-variant microcancers

Background

Papillary thyroid microcarcinomas (mPTCs), tumors less than or equal to 1 cm, have been considered the same clinical entity as microfollicular-variant papillary thyroid microcarcinomas (mFVPTCs). The purpose of this study was to use population-level data to characterize differences between mFVPTC and mPTC.

Materials and methods

We identified adult patients diagnosed with mFVPTC or mPTC between 1998 and 2010 in the Surveillance, Epidemiology, and End Results database. Binary comparisons were made with the Student t-test and chi-squared test. Multivariate logistic regression was used to further analyze lymph node metastases and multifocality.

Results

Of the 30,926 cases, 8697 (28.1%) were mFVPTC. Multifocal tumors occurred with greater frequency in the mFVPTC group compared with the mPTC group (35.4% versus 31.7%; P < 0.01). Multivariate logistic regression indicated that patients with mFVPTC had a 26% increased risk of multifocality (odds ratio, 1.26; 95% confidence interval, 1.2–1.4; P < 0.01). In contrast, lymph node metastases were nearly twice as common in the mPTC group compared with the mFVPTC group (6.8% versus 3.6%; P < 0.01). Multivariate logistic regression confirmed that patients with mPTC had a 69% increased risk of lymph node metastases compared with patients with mFVPTC (odds ratio, 1.69; 95% confidence interval, 1.4–2.0; P < 0.01).

Conclusions

Multifocality is not unique to classical mPTC and occurs more often in mFVPTC. The risk of lymph node metastases is greater for mPTC than mFVPTC. The surgeon should be aware of these features as they may influence the treatment for these microcarcinomas.